Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

. 2023 Feb ; 11 (2) : .

Jazyk angličtina Země Anglie, Velká Británie Médium print

Typ dokumentu časopisecké články, přehledy, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid36822672

Epithelial ovarian cancer (EOC) is among the top five causes of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant cells to the peritoneum. Despite improvements in medical therapies, particularly with the implementation of novel drugs targeting homologous recombination deficiency, the survival rates of patients with EOC remain low. Unlike other neoplasms, EOC remains relatively insensitive to immune checkpoint inhibitors, which is correlated with a tumor microenvironment (TME) characterized by poor infiltration by immune cells and active immunosuppression dominated by immune components with tumor-promoting properties, especially tumor-associated macrophages (TAMs). In recent years, TAMs have attracted interest as potential therapeutic targets by seeking to reverse the immunosuppression in the TME and enhance the clinical efficacy of immunotherapy. Here, we review the key biological features of TAMs that affect tumor progression and their relevance as potential targets for treating EOC. We especially focus on the therapies that might modulate the recruitment, polarization, survival, and functional properties of TAMs in the TME of EOC that can be harnessed to develop superior combinatorial regimens with immunotherapy for the clinical care of patients with EOC.

Zobrazit více v PubMed

Fucikova J, Coosemans A, Orsulic S, et al. . Immunological configuration of ovarian carcinoma: features and impact on disease outcome. J Immunother Cancer 2021;9:e002873. 10.1136/jitc-2021-002873 PubMed DOI PMC

Fucikova J, Palova-Jelinkova L, Klapp V, et al. . Immunological control of ovarian carcinoma by chemotherapy and targeted anticancer agents. Trends Cancer 2022;8:426–44. 10.1016/j.trecan.2022.01.010 PubMed DOI

Sung H, Ferlay J, Siegel RL, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49. 10.3322/caac.21660 PubMed DOI

Lengyel E. Ovarian cancer development and metastasis. Am J Pathol 2010;177:1053–64. 10.2353/ajpath.2010.100105 PubMed DOI PMC

Bowtell DD, Böhm S, Ahmed AA, et al. . Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer 2015;15:668–79. 10.1038/nrc4019 PubMed DOI PMC

Cocetta V, Ragazzi E, Montopoli M. Links between cancer metabolism and cisplatin resistance. Int Rev Cell Mol Biol 2020;354:107–64. 10.1016/bs.ircmb.2020.01.005 PubMed DOI

Poveda A, Floquet A, Ledermann JA, et al. . Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2021;22:620–31. 10.1016/S1470-2045(21)00073-5 PubMed DOI

Rose M, Burgess JT, O’Byrne K, et al. . PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol 2020;8:564601. 10.3389/fcell.2020.564601 PubMed DOI PMC

Perren TJ, Swart AM, Pfisterer J, et al. . A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484–96. 10.1056/NEJMoa1103799 PubMed DOI

Gillyard T, Davis J. DNA double-strand break repair in cancer: A path to achieving precision medicine. Int Rev Cell Mol Biol 2021;364:111–37. 10.1016/bs.ircmb.2021.06.003 PubMed DOI PMC

Curtin NJ, Szabo C. Poly(ADP-ribose) polymerase inhibition: past, present and future. Nat Rev Drug Discov 2020;19:711–36. 10.1038/s41573-020-0076-6 PubMed DOI

González-Martín A, Pothuri B, Vergote I, et al. . Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019;381:2391–402. 10.1056/NEJMoa1910962 PubMed DOI

Wilky BA. Immune checkpoint inhibitors: the linchpins of modern immunotherapy. Immunol Rev 2019;290:6–23. 10.1111/imr.12766 PubMed DOI

Disis ML, Taylor MH, Kelly K, et al. . Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol 2019;5:393–401. 10.1001/jamaoncol.2018.6258 PubMed DOI PMC

Matulonis UA, Shapira-Frommer R, Santin AD, et al. . Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 2019;30:1080–7. 10.1093/annonc/mdz135 PubMed DOI

Johnson RL, Cummings M, Thangavelu A, et al. . Barriers to immunotherapy in ovarian cancer: metabolic, genomic, and immune perturbations in the tumour microenvironment. Cancers (Basel) 2021;13:24. 10.3390/cancers13246231 PubMed DOI PMC

Jayasingam SD, Citartan M, Thang TH, et al. . Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: technicalities and challenges in routine clinical practice. Front Oncol 2019;9:1512. 10.3389/fonc.2019.01512 PubMed DOI PMC

Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol 2020;15:123–47. 10.1146/annurev-pathmechdis-012418-012718 PubMed DOI PMC

Duan Z, Luo Y. Targeting macrophages in cancer immunotherapy. Signal Transduct Target Ther 2021;6:127. 10.1038/s41392-021-00506-6 PubMed DOI PMC

Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014;6:13. 10.12703/P6-13 PubMed DOI PMC

Murray PJ, Allen JE, Biswas SK, et al. . Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41:14–20. 10.1016/j.immuni.2014.06.008 PubMed DOI PMC

Kim SY, Nair MG. Macrophages in wound healing: activation and plasticity. Immunol Cell Biol 2019;97:258–67. 10.1111/imcb.12236 PubMed DOI PMC

Cheng S, Li Z, Gao R, et al. . A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells. Cell 2021;184:792–809. 10.1016/j.cell.2021.01.010 PubMed DOI

Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39–51. 10.1016/j.cell.2010.03.014 PubMed DOI PMC

Wu SZ, Al-Eryani G, Roden DL, et al. . A single-cell and spatially resolved atlas of human breast cancers. Nat Genet 2021;53:1334–47. 10.1038/s41588-021-00911-1 PubMed DOI PMC

Colvin EK. Tumor-Associated macrophages contribute to tumor progression in ovarian cancer. Front Oncol 2014;4:137. 10.3389/fonc.2014.00137 PubMed DOI PMC

Dong P, Ma L, Liu L, et al. . CD86(+)/CD206(+), diametrically polarized tumor-associated macrophages, predict hepatocellular carcinoma patient prognosis. Int J Mol Sci 2016;17:320. 10.3390/ijms17030320 PubMed DOI PMC

Jeong H, Hwang I, Kang SH, et al. . Tumor-Associated macrophages as potential prognostic biomarkers of invasive breast cancer. J Breast Cancer 2019;22:38–51. 10.4048/jbc.2019.22.e5 PubMed DOI PMC

Kawamura K, Komohara Y, Takaishi K, et al. . Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int 2009;59:300–5. 10.1111/j.1440-1827.2009.02369.x PubMed DOI

Xu J, Fang Y, Chen K, et al. . Single-Cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin Cancer Res 2022;28:3590–602. 10.1158/1078-0432.CCR-22-0296 PubMed DOI PMC

Zhang T, Liu Q, Zhu Y, et al. . Lymphocyte and macrophage infiltration in omental metastases indicates poor prognosis in advance stage epithelial ovarian cancer. J Int Med Res 2021;49:03000605211066245. 10.1177/03000605211066245 PubMed DOI PMC

Cotechini T, Atallah A, Grossman A. Tissue-Resident and recruited macrophages in primary tumor and metastatic microenvironments: potential targets in cancer therapy. Cells 2021;10:960. 10.3390/cells10040960 PubMed DOI PMC

Hourani T, Holden JA, Li W, et al. . Tumor associated macrophages: origin, recruitment, phenotypic diversity, and targeting. Front Oncol 2021;11:788365. 10.3389/fonc.2021.788365 PubMed DOI PMC

El-Arabey AA, Denizli M, Kanlikilicer P, et al. . Gata3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma. Cell Signal 2020;68:109539. 10.1016/j.cellsig.2020.109539 PubMed DOI

Hensler M, Kasikova L, Fiser K, et al. . M2-Like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. J Immunother Cancer 2020;8:e000979. 10.1136/jitc-2020-000979 PubMed DOI PMC

Takaishi K, Komohara Y, Tashiro H, et al. . Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via STAT3 activation. Cancer Sci 2010;101:2128–36. 10.1111/j.1349-7006.2010.01652.x PubMed DOI PMC

Wang X, Deavers M, Patenia R, et al. . Monocyte/Macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med 2006;4:30. 10.1186/1479-5876-4-30 PubMed DOI PMC

Yuan X, Zhang J, Li D, et al. . Prognostic significance of tumor-associated macrophages in ovarian cancer: a meta-analysis. Gynecol Oncol 2017;147:181–7. 10.1016/j.ygyno.2017.07.007 PubMed DOI

Steitz AM, Steffes A, Finkernagel F, et al. . Tumor-Associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (Tgfbi) and tenascin C. Cell Death Dis 2020;11:249. 10.1038/s41419-020-2438-8 PubMed DOI PMC

Yin M, Li X, Tan S, et al. . Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. J Clin Invest 2016;126:4157–73. 10.1172/JCI87252 PubMed DOI PMC

Krishnan V, Tallapragada S, Schaar B, et al. . Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1. Commun Biol 2020;3:524. 10.1038/s42003-020-01246-z PubMed DOI PMC

Chen Y, Zhang L, Lv R, et al. . Overexpression of Semaphorin4D indicates poor prognosis and prompts monocyte differentiation toward M2 macrophages in epithelial ovarian cancer. Asian Pac J Cancer Prev 2013;14:5883–90. 10.7314/apjcp.2013.14.10.5883 PubMed DOI

Duluc D, Delneste Y, Tan F, et al. . Tumor-Associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells. Blood 2007;110:4319–30. 10.1182/blood-2007-02-072587 PubMed DOI

Mantovani A, Sozzani S, Locati M, et al. . Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002;23:549–55. 10.1016/s1471-4906(02)02302-5 PubMed DOI

Negus RP, Stamp GW, Relf MG, et al. . The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. J Clin Invest 1995;95:2391–6. 10.1172/JCI117933 PubMed DOI PMC

Sawano A, Iwai S, Sakurai Y, et al. . Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood 2001;97:785–91. 10.1182/blood.v97.3.785 PubMed DOI

Tang M, Liu B, Bu X, et al. . Cross-Talk between ovarian cancer cells and macrophages through periostin promotes macrophage recruitment. Cancer Sci 2018;109:1309–18. 10.1111/cas.13567 PubMed DOI PMC

Kumar S, Mittal S, Gupta P, et al. . Metabolic reprogramming in tumor-associated macrophages in the ovarian tumor microenvironment. Cancers (Basel) 2022;14:21. 10.3390/cancers14215224 PubMed DOI PMC

Larionova I, Kazakova E, Patysheva M, et al. . Transcriptional, epigenetic and metabolic programming of tumor-associated macrophages. Cancers (Basel) 2020;12:1411. 10.3390/cancers12061411 PubMed DOI PMC

Thapa B, Lee K. Metabolic influence on macrophage polarization and pathogenesis. BMB Rep 2019;52:360–72. 10.5483/BMBRep.2019.52.6.140 PubMed DOI PMC

Colegio OR, Chu N-Q, Szabo AL, et al. . Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 2014;513:559–63. 10.1038/nature13490 PubMed DOI PMC

Cramer T, Yamanishi Y, Clausen BE, et al. . Hif-1Alpha is essential for myeloid cell-mediated inflammation. Cell 2003;112:645–57. 10.1016/s0092-8674(03)00154-5 PubMed DOI PMC

Wen Z, Liu H, Li M, et al. . Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration. Oncogene 2015;34:1241–52. 10.1038/onc.2014.85 PubMed DOI

Schumann T, Adhikary T, Wortmann A, et al. . Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget 2015;6:13416–33. 10.18632/oncotarget.3826 PubMed DOI PMC

Goossens P, Rodriguez-Vita J, Etzerodt A, et al. . Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab 2019;29:1376–89. 10.1016/j.cmet.2019.02.016 PubMed DOI

De Nola R, Menga A, Castegna A, et al. . The crowded crosstalk between cancer cells and stromal microenvironment in gynecological malignancies: biological pathways and therapeutic implication. Int J Mol Sci 2019;20:2401. 10.3390/ijms20102401 PubMed DOI PMC

Palmieri EM, Menga A, Martín-Pérez R, et al. . Pharmacologic or genetic targeting of glutamine synthetase skews macrophages toward an M1-like phenotype and inhibits tumor metastasis. Cell Rep 2017;20:1654–66. 10.1016/j.celrep.2017.07.054 PubMed DOI PMC

Curiel TJ, Coukos G, Zou L, et al. . Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942–9. 10.1038/nm1093 PubMed DOI

Laoui D, Van Overmeire E, Di Conza G, et al. . Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res 2014;74:24–30. 10.1158/0008-5472.CAN-13-1196 PubMed DOI

Lecker LSM, Berlato C, Maniati E, et al. . Tgfbi production by macrophages contributes to an immunosuppressive microenvironment in ovarian cancer. Cancer Res 2021;81:5706–19. 10.1158/0008-5472.CAN-21-0536 PubMed DOI PMC

Herrera-Rios D, Mughal SS, Teuber-Hanselmann S, et al. . Macrophages/Microglia represent the major source of indolamine 2,3-dioxygenase expression in melanoma metastases of the brain. Front Immunol 2020;11:120. 10.3389/fimmu.2020.00120 PubMed DOI PMC

Yan H, Dong M, Liu X, et al. . Multiple myeloma cell-derived IL-32γ increases the immunosuppressive function of macrophages by promoting indoleamine 2,3-dioxygenase (IDO) expression. Cancer Lett 2019;446:38–48. 10.1016/j.canlet.2019.01.012 PubMed DOI

Rodriguez PC, Quiceno DG, Zabaleta J, et al. . Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004;64:5839–49. 10.1158/0008-5472.CAN-04-0465 PubMed DOI

Xia H, Li S, Li X, et al. . Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis. JCI Insight 2020;5:e141115. 10.1172/jci.insight.141115 PubMed DOI PMC

Czystowska-Kuzmicz M, Sosnowska A, Nowis D, et al. . Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma. Nat Commun 2019;10:3000. 10.1038/s41467-019-10979-3 PubMed DOI PMC

Gottlieb CE, Mills AM, Cross JV, et al. . Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: a comparison of matched primary and metastatic tumors. Gynecol Oncol 2017;144:607–12. 10.1016/j.ygyno.2016.12.021 PubMed DOI

Kryczek I, Wei S, Zhu G, et al. . Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 2007;67:8900–5. 10.1158/0008-5472.CAN-07-1866 PubMed DOI

Sica GL, Choi IH, Zhu G, et al. . B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 2003;18:849–61. 10.1016/s1074-7613(03)00152-3 PubMed DOI

Zhou J, Li X, Wu X, et al. . Exosomes released from tumor-associated macrophages transfer miRNAs that induce a treg/th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res 2018;6:1578–92. 10.1158/2326-6066.CIR-17-0479 PubMed DOI

Lin EY, Pollard JW. Tumor-Associated macrophages press the angiogenic switch in breast cancer. Cancer Res 2007;67:5064–6. 10.1158/0008-5472.CAN-07-0912 PubMed DOI

Zhu Q, Wu X, Wang X. Differential distribution of tumor-associated macrophages and treg/th17 cells in the progression of malignant and benign epithelial ovarian tumors. Oncol Lett 2017;13:159–66. 10.3892/ol.2016.5428 PubMed DOI PMC

Moughon DL, He H, Schokrpur S, et al. . Macrophage blockade using CSF1R inhibitors reverses the vascular leakage underlying malignant ascites in late-stage epithelial ovarian cancer. Cancer Res 2015;75:4742–52. 10.1158/0008-5472.CAN-14-3373 PubMed DOI PMC

Wang X, Zhu Q, Lin Y, et al. . Crosstalk between tems and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer. Br J Cancer 2017;117:1371–82. 10.1038/bjc.2017.297 PubMed DOI PMC

Yousefzadeh Y, Hallaj S, Baghi Moornani M, et al. . Tumor associated macrophages in the molecular pathogenesis of ovarian cancer. Int Immunopharmacol 2020;84:106471. 10.1016/j.intimp.2020.106471 PubMed DOI

Bekes I, Friedl TWP, Köhler T, et al. . Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? Mol Cancer 2016;15:13. 10.1186/s12943-016-0497-3 PubMed DOI PMC

Shen W, Li H-L, Liu L, et al. . Expression levels of PTEN, HIF-1α, and VEGF as prognostic factors in ovarian cancer. Eur Rev Med Pharmacol Sci 2017;21:2596–603. PubMed

Byrne AT, Ross L, Holash J, et al. . Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 2003;9:5721–8. PubMed

Duyndam MCA, Hilhorst MCGW, Schlüper HMM, et al. . Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and induces cyst formation and macrophage infiltration in human ovarian cancer xenografts. Am J Pathol 2002;160:537–48. 10.1016/s0002-9440(10)64873-0 PubMed DOI PMC

Hagemann T, Wilson J, Kulbe H, et al. . Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol 2005;175:1197–205. 10.4049/jimmunol.175.2.1197 PubMed DOI

Worzfeld T, Pogge von Strandmann E, Huber M, et al. . The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol 2017;7:24. 10.3389/fonc.2017.00024 PubMed DOI PMC

Lane D, Matte I, Laplante C, et al. . Ccl18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling. Mol Cancer 2016;15:58. 10.1186/s12943-016-0542-2 PubMed DOI PMC

Robinson-Smith TM, Isaacsohn I, Mercer CA, et al. . Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res 2007;67:5708–16. 10.1158/0008-5472.CAN-06-4375 PubMed DOI

Carroll MJ, Fogg KC, Patel HA, et al. . Alternatively-activated macrophages upregulate mesothelial expression of P-selectin to enhance adhesion of ovarian cancer cells. Cancer Res 2018;78:3560–73. 10.1158/0008-5472.CAN-17-3341 PubMed DOI PMC

He Y, Zhang M, Wu X, et al. . High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. PLoS One 2013;8:e79769. 10.1371/journal.pone.0079769 PubMed DOI PMC

Le Page C, Marineau A, Bonza PK, et al. . BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PLoS One 2012;7:e38541. 10.1371/journal.pone.0038541 PubMed DOI PMC

Macciò A, Gramignano G, Cherchi MC, et al. . Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients. Sci Rep 2020;10:6096. 10.1038/s41598-020-63276-1 PubMed DOI PMC

Reinartz S, Finkernagel F, Adhikary T, et al. . A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome. Genome Biol 2016;17:108. 10.1186/s13059-016-0956-6 PubMed DOI PMC

Gupta V, Yull F, Khabele D. Bipolar tumor-associated macrophages in ovarian cancer as targets for therapy. Cancers (Basel) 2018;10:366. 10.3390/cancers10100366 PubMed DOI PMC

Yang Y, Yang Y, Yang J, et al. . Tumor microenvironment in ovarian cancer: function and therapeutic strategy. Front Cell Dev Biol 2020;8:758. 10.3389/fcell.2020.00758 PubMed DOI PMC

Zhang M, He Y, Sun X, et al. . A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res 2014;7:19. 10.1186/1757-2215-7-19 PubMed DOI PMC

Liang Y-L, Lin C-N, Tsai H-F, et al. . Omental macrophagic “ crown-like structures ” are associated with poor prognosis in advanced-stage serous ovarian cancer. Curr Oncol 2021;28:4234–46. 10.3390/curroncol28050359 PubMed DOI PMC

Lane D, Matte I, Rancourt C, et al. . Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer 2011;11:210. 10.1186/1471-2407-11-210 PubMed DOI PMC

Reinartz S, Schumann T, Finkernagel F, et al. . Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse. Int J Cancer 2014;134:32–42. 10.1002/ijc.28335 PubMed DOI PMC

Yanaihara N, Anglesio MS, Ochiai K, et al. . Cytokine gene expression signature in ovarian clear cell carcinoma. Int J Oncol 2012;41:1094–100. 10.3892/ijo.2012.1533 PubMed DOI

Qu Q-X, Huang Q, Shen Y, et al. . The increase of circulating PD-L1-expressing CD68 (+) macrophage in ovarian cancer. Tumour Biol 2016;37:5031–7. 10.1007/s13277-015-4066-y PubMed DOI

Liu C, Zhang Y, Li X, et al. . Ovarian cancer-specific dysregulated genes with prognostic significance: scrna-seq with bulk RNA-seq data and experimental validation. Ann N Y Acad Sci 2022;1512:154–73. 10.1111/nyas.14748 PubMed DOI

Finkernagel F, Reinartz S, Lieber S, et al. . The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. Oncotarget 2016;7:75339–52. 10.18632/oncotarget.12180 PubMed DOI PMC

Tan Q, Liu H, Xu J, et al. . Integrated analysis of tumor-associated macrophage infiltration and prognosis in ovarian cancer. Aging (Albany NY) 2021;13:23210–32. 10.18632/aging.203613 PubMed DOI PMC

Adhikary T, Wortmann A, Finkernagel F, et al. . Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients. BMC Genomics 2017;18:243. 10.1186/s12864-017-3630-9 PubMed DOI PMC

Worzfeld T, Finkernagel F, Reinartz S, et al. . Proteotranscriptomics reveal signaling networks in the ovarian cancer microenvironment. Mol Cell Proteomics 2018;17:270–89. 10.1074/mcp.RA117.000400 PubMed DOI PMC

Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 2018;118:9–16. 10.1038/bjc.2017.434 PubMed DOI PMC

Weissleder R, Pittet MJ. The expanding landscape of inflammatory cells affecting cancer therapy. Nat Biomed Eng 2020;4:489–98. 10.1038/s41551-020-0524-y PubMed DOI PMC

Arlauckas SP, Garris CS, Kohler RH, et al. . In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med 2017;9:eaal3604. 10.1126/scitranslmed.aal3604 PubMed DOI PMC

Xu Y, Zuo F, Wang H, et al. . The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer. Front Immunol 2022;13:1045957. 10.3389/fimmu.2022.1045957 PubMed DOI PMC

Pujade-Lauraine E, Fujiwara K, Ledermann JA, et al. . Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (javelin ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol 2021;22:1034–46. 10.1016/S1470-2045(21)00216-3 PubMed DOI

Yang M, Lu J, Zhang G, et al. . Cxcl13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer. J Immunother Cancer 2021;9:e001136. 10.1136/jitc-2020-001136 PubMed DOI PMC

Vlaming M, Bilemjian V, Freile JÁ, et al. . Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival. Front Immunol 2022;13:1031746. 10.3389/fimmu.2022.1031746 PubMed DOI PMC

Färkkilä A, Gulhan DC, Casado J, et al. . Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun 2020;11:1459. 10.1038/s41467-020-15315-8 PubMed DOI PMC

Ni Y, Soliman A, Joehlin-Price A, et al. . High TGF-β signature predicts immunotherapy resistance in gynecologic cancer patients treated with immune checkpoint inhibition. NPJ Precis Oncol 2021;5:101. 10.1038/s41698-021-00242-8 PubMed DOI PMC

Chambers SK, Kacinski BM, Ivins CM, et al. . Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1. Clin Cancer Res 1997;3:999–1007. PubMed

Stanley ER, Chitu V. Csf-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol 2014;6:a021857. 10.1101/cshperspect.a021857 PubMed DOI PMC

Akkari L, Bowman RL, Tessier J, et al. . Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance. Sci Transl Med 2020;12:eaaw7843. 10.1126/scitranslmed.aaw7843 PubMed DOI

Pfirschke C, Zilionis R, Engblom C, et al. . Macrophage-Targeted therapy unlocks antitumoral cross-talk between ifnγ-secreting lymphocytes and IL12-producing dendritic cells. Cancer Immunol Res 2022;10:40–55. 10.1158/2326-6066.CIR-21-0326 PubMed DOI PMC

Ries CH, Cannarile MA, Hoves S, et al. . Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 2014;25:846–59. 10.1016/j.ccr.2014.05.016 PubMed DOI

Gomez-Roca CA, Italiano A, Le Tourneau C, et al. . Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages. Ann Oncol 2019;30:1381–92. 10.1093/annonc/mdz163 PubMed DOI PMC

Machiels J-P, Gomez-Roca C, Michot J-M, et al. . Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients. J Immunother Cancer 2020;8:e001153. 10.1136/jitc-2020-001153 PubMed DOI PMC

Falchook GS, Peeters M, Rottey S, et al. . A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Invest New Drugs 2021;39:1284–97. 10.1007/s10637-021-01088-4 PubMed DOI

Cannarile MA, Weisser M, Jacob W, et al. . Colony-Stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer 2017;5:53. 10.1186/s40425-017-0257-y PubMed DOI PMC

Lim SY, Yuzhalin AE, Gordon-Weeks AN, et al. . Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget 2016;7:28697–710. 10.18632/oncotarget.7376 PubMed DOI PMC

Qian B-Z, Li J, Zhang H, et al. . Ccl2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 2011;475:222–5. 10.1038/nature10138 PubMed DOI PMC

Moisan F, Francisco EB, Brozovic A, et al. . Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers. Mol Oncol 2014;8:1231–9. 10.1016/j.molonc.2014.03.016 PubMed DOI PMC

Brana I, Calles A, LoRusso PM, et al. . Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol 2015;10:111–23. 10.1007/s11523-014-0320-2 PubMed DOI

Sandhu SK, Papadopoulos K, Fong PC, et al. . A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), A human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol 2013;71:1041–50. 10.1007/s00280-013-2099-8 PubMed DOI

Hyman DM, Rizvi N, Natale R, et al. . Phase I study of MEDI3617, a selective angiopoietin-2 inhibitor alone and combined with carboplatin/paclitaxel, paclitaxel, or bevacizumab for advanced solid tumors. Clin Cancer Res 2018;24:2749–57. 10.1158/1078-0432.CCR-17-1775 PubMed DOI PMC

Vergote I, Scambia G, O’Malley DM, et al. . Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial. Lancet Oncol 2019;20:862–76. 10.1016/S1470-2045(19)30178-0 PubMed DOI

Hidalgo M, Martinez-Garcia M, Le Tourneau C, et al. . First-In-Human phase I study of single-agent vanucizumab, a first-in-class bispecific anti-angiopoietin-2/anti-VEGF-A antibody, in adult patients with advanced solid tumors. Clin Cancer Res 2018;24:1536–45. 10.1158/1078-0432.CCR-17-1588 PubMed DOI

Kobayashi Y, Kashima H, Rahmanto YS, et al. . Drug repositioning of mevalonate pathway inhibitors as antitumor agents for ovarian cancer. Oncotarget 2017;8:72147–56. 10.18632/oncotarget.20046 PubMed DOI PMC

Reusser NM, Dalton HJ, Pradeep S, et al. . Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer. Cancer Biol Ther 2014;15:1061–7. 10.4161/cbt.29184 PubMed DOI PMC

Germano G, Frapolli R, Belgiovine C, et al. . Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 2013;23:249–62. 10.1016/j.ccr.2013.01.008 PubMed DOI

Rodriguez-Garcia A, Lynn RC, Poussin M, et al. . Car-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat Commun 2021;12:877. 10.1038/s41467-021-20893-2 PubMed DOI PMC

Binnewies M, Pollack JL, Rudolph J, et al. . Targeting TREM2 on tumor-associated macrophages enhances immunotherapy. Cell Rep 2021;37:109844. 10.1016/j.celrep.2021.109844 PubMed DOI

Molgora M, Esaulova E, Vermi W, et al. . TREM2 modulation remodels the tumor myeloid landscape enhancing anti-PD-1 immunotherapy. Cell 2020;182:886–900. 10.1016/j.cell.2020.07.013 PubMed DOI PMC

Pittet MJ, Michielin O, Migliorini D. Clinical relevance of tumour-associated macrophages. Nat Rev Clin Oncol 2022;19:402–21. 10.1038/s41571-022-00620-6 PubMed DOI

Pahlavanneshan S, Sayadmanesh A, Ebrahimiyan H, et al. . Toll-like receptor-based strategies for cancer immunotherapy. J Immunol Res 2021;2021:9912188. 10.1155/2021/9912188 PubMed DOI PMC

Geller MA, Cooley S, Argenta PA, et al. . Toll-like receptor-7 agonist administered subcutaneously in a prolonged dosing schedule in heavily pretreated recurrent breast, ovarian, and cervix cancers. Cancer Immunol Immunother 2010;59:1877–84. 10.1007/s00262-010-0914-1 PubMed DOI PMC

Monk BJ, Brady MF, Aghajanian C, et al. . A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: A gynecologic oncology group partners study. Ann Oncol 2017;28:996–1004. 10.1093/annonc/mdx049 PubMed DOI PMC

Kang Y, Flores L, Ngai HW, et al. . Large, anionic liposomes enable targeted intraperitoneal delivery of a TLR 7/8 agonist to repolarize ovarian tumors’ microenvironment. Bioconjug Chem 2021;32:1581–92. 10.1021/acs.bioconjchem.1c00139 PubMed DOI

Le F, Yang L, Han Y, et al. . TPL inhibits the invasion and migration of drug-resistant ovarian cancer by targeting the PI3K/AKT/NF-κb-signaling pathway to inhibit the polarization of M2 tams. Front Oncol 2021;11:704001. 10.3389/fonc.2021.704001 PubMed DOI PMC

Meng C, Zhu H, Song H, et al. . Targets and molecular mechanisms of triptolide in cancer therapy. Chin J Cancer Res 2014;26:622–6. 10.3978/j.issn.1000-9604.2014.09.01 PubMed DOI PMC

Kaneda MM, Messer KS, Ralainirina N, et al. . PI3Kγ is a molecular switch that controls immune suppression. Nature 2016;539:437–42. 10.1038/nature19834 PubMed DOI PMC

De Henau O, Rausch M, Winkler D, et al. . Overcoming resistance to checkpoint blockade therapy by targeting pi3kγ in myeloid cells. Nature 2016;539:443–7. 10.1038/nature20554 PubMed DOI PMC

Suttles J, Stout RD. Macrophage CD40 signaling: a pivotal regulator of disease protection and pathogenesis. Semin Immunol 2009;21:257–64. 10.1016/j.smim.2009.05.011 PubMed DOI

Beatty GL, Chiorean EG, Fishman MP, et al. . CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011;331:1612–6. 10.1126/science.1198443 PubMed DOI PMC

Kashyap AS, Schmittnaegel M, Rigamonti N, et al. . Optimized antiangiogenic reprogramming of the tumor microenvironment potentiates CD40 immunotherapy. Proc Natl Acad Sci U S A 2020;117:541–51. 10.1073/pnas.1902145116 PubMed DOI PMC

Garris CS, Arlauckas SP, Kohler RH, et al. . Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12. Immunity 2018;49:1148–61. 10.1016/j.immuni.2018.09.024 PubMed DOI PMC

Vonderheide RH, Burg JM, Mick R, et al. . Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology 2013;2:e23033. 10.4161/onci.23033 PubMed DOI PMC

Ye S, Cohen D, Belmar NA, et al. . A bispecific molecule targeting CD40 and tumor antigen mesothelin enhances tumor-specific immunity. Cancer Immunol Res 2019;7:1864–75. 10.1158/2326-6066.CIR-18-0805 PubMed DOI

Kuhn NF, Purdon TJ, van Leeuwen DG, et al. . Cd40 ligand-modified chimeric antigen receptor T cells enhance antitumor function by eliciting an endogenous antitumor response. Cancer Cell 2019;35:473–88. 10.1016/j.ccell.2019.02.006 PubMed DOI PMC

Eriksson E, Milenova I, Wenthe J, et al. . Shaping the tumor stroma and sparking immune activation by CD40 and 4-1BB signaling induced by an armed oncolytic virus. Clin Cancer Res 2017;23:5846–57. 10.1158/1078-0432.CCR-17-0285 PubMed DOI

Duluc D, Corvaisier M, Blanchard S, et al. . Interferon-Gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int J Cancer 2009;125:367–73. 10.1002/ijc.24401 PubMed DOI

Castro F, Cardoso AP, Gonçalves RM, et al. . Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol 2018;9:847. 10.3389/fimmu.2018.00847 PubMed DOI PMC

Sun Y. Therapeutic effect of recombinant plasmid-encoded human interleukin-12 in tumor-bearing mice. Mol Med Rep 2012;6:645–50. 10.3892/mmr.2012.973 PubMed DOI

Anwer K, Barnes MN, Fewell J, et al. . Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer. Gene Ther 2010;17:360–9. 10.1038/gt.2009.159 PubMed DOI

Anwer K, Kelly FJ, Chu C, et al. . Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 2013;131:169–73. 10.1016/j.ygyno.2013.07.081 PubMed DOI

Thaker PH, Bradley WH, Leath CA, et al. . GEN-1 in combination with neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer: A phase I dose-escalation study. Clin Cancer Res 2021;27:5536–45. 10.1158/1078-0432.CCR-21-0360 PubMed DOI PMC

Spear P, Barber A, Rynda-Apple A, et al. . Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-γ and GM-CSF. J Immunol 2012;188:6389–98. 10.4049/jimmunol.1103019 PubMed DOI PMC

Chmielewski M, Kopecky C, Hombach AA, et al. . IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res 2011;71:5697–706. 10.1158/0008-5472.CAN-11-0103 PubMed DOI

Brempelis KJ, Cowan CM, Kreuser SA, et al. . Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses. J Immunother Cancer 2020;8:e001356. 10.1136/jitc-2020-001356 PubMed DOI PMC

Klichinsky M, Ruella M, Shestova O, et al. . Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020;38:947–53. 10.1038/s41587-020-0462-y PubMed DOI PMC

Hochreiter-Hufford A, Ravichandran KS. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol 2013;5:a008748. 10.1101/cshperspect.a008748 PubMed DOI PMC

Brightwell RM, Grzankowski KS, Lele S, et al. . The CD47 “ do’n’t eat me signal” is highly expressed in human ovarian cancer. Gynecol Oncol 2016;143:393–7. 10.1016/j.ygyno.2016.08.325 PubMed DOI PMC

Kristiansen G, Denkert C, Schlüns K, et al. . Cd24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 2002;161:1215–21. 10.1016/S0002-9440(10)64398-2 PubMed DOI PMC

Liu R, Wei H, Gao P, et al. . Cd47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis. Oncotarget 2017;8:39021–32. 10.18632/oncotarget.16547 PubMed DOI PMC

Nakamura K, Terai Y, Tanabe A, et al. . Cd24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways. Oncol Rep 2017;37:3189–200. 10.3892/or.2017.5583 PubMed DOI PMC

Barkal AA, Brewer RE, Markovic M, et al. . Cd24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature 2019;572:392–6. 10.1038/s41586-019-1456-0 PubMed DOI PMC

Osborn G, Stavraka C, Adams R, et al. . Macrophages in ovarian cancer and their interactions with monoclonal antibody therapies. Clin Exp Immunol 2022;209:4–21. 10.1093/cei/uxab020 PubMed DOI PMC

Sikic BI, Lakhani N, Patnaik A, et al. . First-in-human, first-in-class phase I trial of the anti-CD47 antibody hu5f9-G4 in patients with advanced cancers. J Clin Oncol 2019;37:946–53. 10.1200/JCO.18.02018 PubMed DOI PMC

Mbongue JC, Nicholas DA, Torrez TW, et al. . The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines (Basel) 2015;3:703–29. 10.3390/vaccines3030703 PubMed DOI PMC

Uyttenhove C, Pilotte L, Théate I, et al. . Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003;9:1269–74. 10.1038/nm934 PubMed DOI

Okamoto A, Nikaido T, Ochiai K, et al. . Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res 2005;11:6030–9. 10.1158/1078-0432.CCR-04-2671 PubMed DOI

Tanizaki Y, Kobayashi A, Toujima S, et al. . Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment. Cancer Sci 2014;105:966–73. 10.1111/cas.12445 PubMed DOI PMC

Ma H, Qin Q, Mi J, et al. . 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function. BMC Pharmacol Toxicol 2020;21:67. 10.1186/s40360-020-00439-w PubMed DOI PMC

Komiya T, Huang CH. Updates in the clinical development of epacadostat and other indoleamine 2,3-dioxygenase 1 inhibitors (IDO1) for human cancers. Front Oncol 2018;8:423. 10.3389/fonc.2018.00423 PubMed DOI PMC

Mitchell TC, Hamid O, Smith DC, et al. . Epacadostat plus pembrolizumab in patients with advanced solid tumors: phase I results from a multicenter, open-label phase I/II trial (ECHO-202/KEYNOTE-037). J Clin Oncol 2018;36:3223–30. 10.1200/JCO.2018.78.9602 PubMed DOI PMC

Nayak-Kapoor A, Hao Z, Sadek R, et al. . Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors. J Immunother Cancer 2018;6:61. 10.1186/s40425-018-0351-9 PubMed DOI PMC

Kristeleit R, Davidenko I, Shirinkin V, et al. . A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer. Gynecol Oncol 2017;146:484–90. 10.1016/j.ygyno.2017.07.005 PubMed DOI

Odunsi K, Qian F, Lugade AA, et al. . Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses. Sci Transl Med 2022;14:eabg8402. 10.1126/scitranslmed.abg8402 PubMed DOI PMC

Hamanishi J, Mandai M, Iwasaki M, et al. . Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 2007;104:3360–5. 10.1073/pnas.0611533104 PubMed DOI PMC

Topalian SL, Hodi FS, Brahmer JR, et al. . Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab. JAMA Oncol 2019;5:1411–20. 10.1001/jamaoncol.2019.2187 PubMed DOI PMC

Tseng SY, Otsuji M, Gorski K, et al. . B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 2001;193:839–46. 10.1084/jem.193.7.839 PubMed DOI PMC

Zou W, Wolchok JD, Chen L. Pd-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med 2016;8:328rv4. 10.1126/scitranslmed.aad7118 PubMed DOI PMC

Hartley GP, Chow L, Ammons DT, et al. . Programmed cell death ligand 1 (PD-L1) signaling regulates macrophage proliferation and activation. Cancer Immunol Res 2018;6:1260–73. 10.1158/2326-6066.CIR-17-0537 PubMed DOI

Liu JF, Gordon M, Veneris J, et al. . Safety, clinical activity and biomarker assessments of atezolizumab from a phase I study in advanced/recurrent ovarian and uterine cancers. Gynecol Oncol 2019;154:314–22. 10.1016/j.ygyno.2019.05.021 PubMed DOI

Lee EK, Konstantinopoulos PA. Parp inhibition and immune modulation: scientific rationale and perspectives for the treatment of gynecologic cancers. Ther Adv Med Oncol 2020;12:1758835920944116. 10.1177/1758835920944116 PubMed DOI PMC

Li A, Yi M, Qin S, et al. . Prospects for combining immune checkpoint blockade with PARP inhibition. J Hematol Oncol 2019;12:98. 10.1186/s13045-019-0784-8 PubMed DOI PMC

Pilié PG, Gay CM, Byers LA, et al. . Parp inhibitors: extending benefit beyond BRCA-mutant cancers. Clin Cancer Res 2019;25:3759–71. 10.1158/1078-0432.CCR-18-0968 PubMed DOI

Jiao S, Xia W, Yamaguchi H, et al. . Parp inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 2017;23:3711–20. 10.1158/1078-0432.CCR-16-3215 PubMed DOI PMC

Domchek SM, Postel-Vinay S, Im S-A, et al. . Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol 2020;21:1155–64. 10.1016/S1470-2045(20)30324-7 PubMed DOI

Lee J-M, Cimino-Mathews A, Peer CJ, et al. . Safety and clinical activity of the programmed death-ligand 1 inhibitor durvalumab in combination with poly (ADP-ribose) polymerase inhibitor olaparib or vascular endothelial growth factor receptor 1-3 inhibitor cediranib in women’s cancers: a dose-escalation, phase I study. J Clin Oncol 2017;35:2193–202. 10.1200/JCO.2016.72.1340 PubMed DOI PMC

Lampert EJ, Zimmer A, Padget M, et al. . Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase II study. Clin Cancer Res 2020;26:4268–79. 10.1158/1078-0432.CCR-20-0056 PubMed DOI PMC

Shrimali RK, Yu Z, Theoret MR, et al. . Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res 2010;70:6171–80. 10.1158/0008-5472.CAN-10-0153 PubMed DOI PMC

Liu JF, Herold C, Gray KP, et al. . Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: A phase 2 clinical trial. JAMA Oncol 2019;5:1731–8. 10.1001/jamaoncol.2019.3343 PubMed DOI PMC

Giornelli GH. Management of relapsed ovarian cancer: a review. Springerplus 2016;5:1197. 10.1186/s40064-016-2660-0 PubMed DOI PMC

Haibe Y, Kreidieh M, El Hajj H, et al. . Resistance mechanisms to anti-angiogenic therapies in cancer. Front Oncol 2020;10:221. 10.3389/fonc.2020.00221 PubMed DOI PMC

Lyons YA, Pradeep S, Wu SY, et al. . Macrophage depletion through colony stimulating factor 1 receptor pathway blockade overcomes adaptive resistance to anti-VEGF therapy. Oncotarget 2017;8:96496–505. 10.18632/oncotarget.20410 PubMed DOI PMC

Rivera LB, Meyronet D, Hervieu V, et al. . Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy. Cell Rep 2015;11:577–91. 10.1016/j.celrep.2015.03.055 PubMed DOI PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...