The Role of Tumor Microenvironment and Immune Response in Colorectal Cancer Development and Prognosis
Jazyk angličtina Země Švýcarsko Médium electronic-ecollection
Typ dokumentu časopisecké články, přehledy
PubMed
35936516
PubMed Central
PMC9350736
DOI
10.3389/pore.2022.1610502
PII: 1610502
Knihovny.cz E-zdroje
- Klíčová slova
- colorectal cancer, consensus molecular subtypes, immune cells, immunoscore, tumor microenvironment, tumorigenesis,
- MeSH
- imunita MeSH
- imunoterapie MeSH
- kolorektální nádory * patologie MeSH
- lidé MeSH
- nádorové mikroprostředí * MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Colorectal cancer (CRC) is one of the most common cancers worldwide. The patient's prognosis largely depends on the tumor stage at diagnosis. The pathological TNM Classification of Malignant Tumors (pTNM) staging of surgically resected cancers represents the main prognostic factor and guidance for decision-making in CRC patients. However, this approach alone is insufficient as a prognostic predictor because clinical outcomes in patients at the same histological tumor stage can still differ. Recently, significant progress in the treatment of CRC has been made due to improvements in both chemotherapy and surgical management. Immunotherapy-based approaches are one of the most rapidly developing areas of tumor therapy. This review summarizes the current knowledge about the tumor microenvironment (TME), immune response and its interactions with CRC development, immunotherapy and prognosis.
Zobrazit více v PubMed
Creasy JM, Sadot E, Koerkamp BG, Chou JF, Gonen M, Kemeny NE, et al. Actual 10-year Survival after Hepatic Resection of Colorectal Liver Metastases: What Factors Preclude Cure? Surgery (2018) 163:1238–44. 10.1016/j.surg.2018.01.004 PubMed DOI PMC
Tomášek J, Kiss I. Immunotherapy of Colorectal and Anal Cancer. Klin Onkol (2017) 30(3):3562–5. 10.14735/amko20173S62 PubMed DOI
Grady WM, Pritchard CC. Molecular Alterations and Biomarkers in Colorectal Cancer. Toxicol Pathol (2014) 42:124–39. 10.1177/0192623313505155 PubMed DOI PMC
McGranahan N, Furness AJS, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal Neoantigens Elicit T Cell Immunoreactivity and Sensitivity to Immune Checkpoint Blockade. Science (2016) 351(6280):1463–9. 10.1126/science.aaf1490 PubMed DOI PMC
Tsang AHF, Cheng KH, Wong ASP, Ng SS, Ma BB, Chan CML, et al. Current and Future Molecular Diagnostics in Colorectal Cancer and Colorectal Adenoma. World J Gastroenterol (2014) 20:3847–57. 10.3748/wjg.v20.i14.3847 PubMed DOI PMC
Damilakis E, Mavroudis D, Sfakianaki M, Souglakos J. Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival? Cancers (2020) 12:889. 10.3390/cancers12040889 PubMed DOI PMC
Advani SM, Advani PS, Brown DW, DeSantis SM, Korphaisarn K, VonVille HM, et al. Global Differences in the Prevalence of the CpG Island Methylator Phenotype of Colorectal Cancer. BMC Cancer (2019) 19:964. 10.1186/s12885-019-6144-9 PubMed DOI PMC
Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The Consensus Molecular Subtypes of Colorectal Cancer. Nat Med (2015) 21:1350–6. 10.1038/nm.3967 PubMed DOI PMC
Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability. J Natl Cancer Inst (2004) 96:261–8. 10.1093/jnci/djh034 PubMed DOI PMC
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The Vigorous Immune Microenvironment of Microsatellite Instable colon Cancer is Balanced by Multiple Counter-inhibitory Checkpoints. Cancer Discov (2015) 5(1):43–51. 10.1158/2159-8290.CD-14-0863 PubMed DOI PMC
Fridman WH, Zitvogel L, Sautes-Fridman C, Kroemer G. The Immune Contexture in Cancer Prognosis and Treatment. Nat Rev Clin Oncol (2017) 14:717–34. 10.1038/nrclinonc.2017.101 PubMed DOI
Fiegle E, Doleschel D, Koletnik S, Rix A, Weiskirchen R, Borkham-Kamphorst E, et al. Dual CTLA-4 and PD-L1 Blockade Inhibits Tumor Growth and Liver Metastasis in a Highly Aggressive Orthotopic Mouse Model of Colon Cancer. Neoplasia (2019) 21:932–44. 10.1016/j.neo.2019.07.006 PubMed DOI PMC
Imai K, Yamamoto H. Carcinogenesis and Microsatellite Instability: The Interrelationship between Genetics and Epigenetics. Carcinogenesis (2008) 29:673–80. 10.1093/carcin/bgm228 PubMed DOI
Lynch H, Lynch P, Lanspa S, Snyder C, Lynch J, Boland C, et al. Review of the Lynch Syndrome: History, Molecular Genetics, Screening, Differential Diagnosis, and Medicolegal Ramifications. Clin Genet (2009) 76:1–18. 10.1111/j.1399-0004.2009.01230.x PubMed DOI PMC
Jenkins MA, Hayashi S, O´Shea AM, Burgart LJ, Smyrk TC, Shimizu D, et al. Pathology Features in Bethesda Guidelines Predict Colorectal Cancer Microsatellite Instability: A Population-Based Study. Gastroenterology (2007) 133:48–56. 10.1053/j.gastro.2007.04.044 PubMed DOI PMC
Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, et al. Tumor-infiltrating T-Cell Subsets, Molecular Changes in Colorectal Cancer, and Prognosis: Cohort Study and Literature Review. J Pathol (2010) 12:298–306. 10.1002/path.2774 PubMed DOI PMC
Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, et al. Lymphocytic Reaction to Colorectal Cancer is Associated with Longer Survival, Independent of Lymph Node Count, Microsatellite Instability, and CpG Island Methylator Phenotype. Clin Cancer Res (2009) 15:6412–20. 10.1158/1078-0432.CCR-09-1438 PubMed DOI PMC
Fabrizio DA, George TJ, Dunne RF, Frampton G, Sun J, Gowen K, et al. Beyond Microsatellite Testing: Assessment of Tumor Mutational burden Identifies Subsets of Colorectal Cancer Who May Respond to Immune Checkpoint Inhibition. J Gastrointest Oncol (2018) 9(4):610–7. 10.21037/jgo.2018.05.06 PubMed DOI PMC
Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, et al. Tumor-infiltrating FOXP3+ T Regulatory Cells Show strong Prognostic Significance in Colorectal Cancer. J Clin Oncol (2009) 27:186–92. 10.1200/JCO.2008.18.7229 PubMed DOI
Angell HK, Bruni D, Barett JC, Herbst R, Galon J. The Immunoscore: Colon Cancer and beyond. Clin Cancer Res (2020) 26:332–9. 10.1158/1078-0432.CCR-18-1851 PubMed DOI
Krummel MF, Allison JP. CD28 and CTLA-4 Have Opposing Effects on the Response of T Cells to Stimulation. J Exp Med (1995) 182:459–65. 10.1084/jem.182.2.459 PubMed DOI PMC
Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer. N Engl J Med (2012) 366(26):2455–65. 10.1056/NEJMoa1200694 PubMed DOI PMC
Pardoll DM. The Blockade of Immune Checkpoints in Cancer Immunotherapy. Nat Rev Cancer (2012) 4:252–64. 10.1038/nrc3239 PubMed DOI PMC
Han Y, Yang Y, Chen Z, Jiang Z, Gu Y, Liu Y, et al. Human Hepatocellular Carcinoma-Infiltrating CD4+ CD69+ Foxp3- Regulatory T Cell Suppresses T Cell Response via Membrane-Bound TGF-Beta1. J Mol Med (2014) 95(5):539–50. 10.1007/s00109-014-1143-4 PubMed DOI
Svensson H, Olofsson V, Lundin S, Yakkala C, Bjorck S, Borjesson L, et al. Accumulation of CCR4+CTLA-4hi FOXP3+CD25hi Regulatory T Cells in colon Adenocarcinomas Correlate to Reduced Activation of Conventional T Cells. PLoS One (2012) 7:e30695. 10.1371/journal.pone.0030695 PubMed DOI PMC
Liu Y, Xia T, Jin CH, Gu D, Yu J, Shi W, et al. FOXP3 and CEACAM6 Expression and T Cell Infiltration in the Occurrence and Development of colon Cancer. Oncol Lett (2016) 11:3693–701. 10.3892/ol.2016.4439 PubMed DOI PMC
Deschoolmeester V, Baay M, Lardon F, Pauwels P, Peeters M. Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI. Cancer Microenviron (2011) 4:377–92. 10.1007/s12307-011-0068-5 PubMed DOI PMC
Xu W, Liu H, Song J, Fu HX, Qiu L, Zhang BF, et al. The Appearance of Tregs in Cancer Nest is a Promising Independent Risk Factor in colon Cancer. J Cancer Res Clin Oncol (2013) 139:1845–52. 10.1007/s00432-013-1500-7 PubMed DOI
Poschke I, Mougiakakos D, Kiessling R. Camouflage and Sabotage: Tumor Escape from the Immune System. Cancer Immunol Immunother (2011) 60:1161–71. 10.1007/s00262-011-1012-8 PubMed DOI PMC
Fife BT, Bluestone JA. Control of Peripheral T-Cell Tolerance and Autoimmunity via the CTLA-4 and PD-1 Pathways. Immunol Rev (2008) 224:166–82. 10.1111/j.1600-065X.2008.00662.x PubMed DOI
Takasu C, Nishi M, Yoshikawa K, Tokunaga T, Kashihara H, Yoshimoto T, et al. Impact of Sidedness of Colorectal Cancer on Tumor Immunity. PLoS ONE (2020) 15(10):e0240408. 10.1371/journal.pone.0240408 PubMed DOI PMC
Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY, et al. Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3. Immunity (2005) 22:329–41. 10.1016/j.immuni.2005.01.016 PubMed DOI
Li W, Wang L, Katoh H, Liu R, Zheng P, Liu Y, et al. Identification of a Tumor Suppressor Relay between the FOXP3 and the Hippo Pathways in Breast and Prostate Cancers. Cancer Res (2011) 71:2162–71. 10.1158/0008-5472.CAN-10-3268 PubMed DOI PMC
Zuo T, Liu R, Zhang H, Chang X, Liu Y, Wang L, et al. FOXP3 is a Novel Transcriptional Repressor for the Breast Cancer Oncogene SKP2. J Clin Invest (2007) 117:3765–73. 10.1172/JCI32538 PubMed DOI PMC
Kim M, Grimmig T, Grimm M, Lazariotou M, Meier E, Rosenwald A, et al. Expression of Foxp3 in Colorectal Cancer but Not in Treg Cells Correlates with Disease Progression in Patients with Colorectal Cancer. PLoS One (2013) 8(1):e53630. 10.1371/journal.pone.0053630 PubMed DOI PMC
Yoon HH, Orrock JM, Foster NR, Sargent DJ, Smyrk TC, Sinicrope FA, et al. Prognostic Impact of FoxP3+ Regulatory T Cells in Relation to CD8+ T Lymphocyte Density in Human Colon Carcinomas. PLoS ONE (2012) 7(8):e42274. 10.1371/journal.pone.0042274 PubMed DOI PMC
Ling A, Edin S, Wikberg ML, Öberg Å, Palmqvist R. The Intratumoural Subsite and Relation of CD8(+) and FOXP3(+) T Lymphocytes in Colorectal Cancer Provide Important Prognostic Clues. Br J Cancer (2014) 110:2551–9. 10.1038/bjc.2014.161 PubMed DOI PMC
Ladoire S, Martin F, Ghiringhelli F. Prognostic Role of FOXP3+ Regulatory T Cells Infiltrating Human Carcinomas: The Paradox of Colorectal Cancer. Cancer Immunol Immunother (2011) 60(7):909–18. 10.1007/s00262-011-1046-y PubMed DOI PMC
Sharpe AH, Pauken KE. The Diverse Functions of the PD1 Inhibitory Pathway. Nat Rev Immunol (2018) 18:153–67. 10.1038/nri.2017.108 PubMed DOI
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its Ligands in Tolerance and Immunity. Annu Rev Immunol (2008) 26:677–704. 10.1146/annurev.immunol.26.021607.090331 PubMed DOI PMC
Okazaki T, Honjo T. The PD-1-PD-L Pathway in Immunological Tolerance. Trends Immunol (2006) 27:195–201. 10.1016/j.it.2006.02.001 PubMed DOI
Bardhan K, Anagnostou T, Boussiotis VA. The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation. Front Immunol (2016) 7:550. 10.3389/fimmu.2016.00550 PubMed DOI PMC
Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 Costimulation: A Review. Crit Rev Immunol (1998) 18(5):389–418. 10.1615/critrevimmunol.v18.i5.10 PubMed DOI
Calik I, Calik M, Turken G, Ozercan IH, Dagli AF, Artas G, et al. Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer. Medicina (2019) 55:723. 10.3390/medicina55110723 PubMed DOI PMC
Berntsson J, Eberhard J, Nodin B, Leandersson K, Larsson AH, Jirström K, et al. Expression of Programmed Cell Death Protein 1 (PD-1) and its Ligand PD-L1 in Colorectal Cancer: Relationship with Sidedness and Prognosis. Oncoloimmunology (2018) 7:e1465165. 10.1080/2162402X.2018.1465165 PubMed DOI PMC
Yi M, Niu M, Xu L, Luo S, Wu K. Regulation of PD-L1 Expression in the Tumor Microenvironment. J Hematol Oncol (2021) 14:10. 10.1186/s13045-020-01027-5 PubMed DOI PMC
Akinleye A, Rasool Z. Immune Checkpoint Inhibitors of PD-L1 as Cancer Therapeutics. J Hematol Oncol (2019) 12:92. 10.1186/s13045-019-0779-5 PubMed DOI PMC
Noh BJ, Kwak JY, Eom DW. Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma. BMC Cancer (2020) 20:58. 10.1186/s12885-020-6553-9 PubMed DOI PMC
Panda A, Betigeri A, Subramanian K, Ross JS, Pavlick DC, Ali S, et al. Identifying a Clinically Applicable Mutational Burden Threshold as a Potential Biomarker of Response to Immune Checkpoint Therapy in Solid Tumors. JCO Precis Oncol (2017) 2017:1–13. 10.1200/PO.17.00146 PubMed DOI PMC
Liu S, Gӧnen M, Stadler ZK, Weiser MR, Hechtman JF, Vakiani E, et al. Cellular Localization of PD-L1 Expression in Mismatch-Repair-Deficient and Proficient Colorectal Carcinomas. Mod Pathol (2019) 32:110–21. 10.1038/s41379-018-0114-7 PubMed DOI PMC
Li Y, Liang L, Dai W, Cai G, Xu Y, Li X, et al. Prognostic Impact of Programed Cell Death-1 (PD-1) and PD-Ligand 1 (PD-L1) Expression in Cancer Cells and Tumor Infiltrating Lymphocytes in Colorectal Cancer. Mol Cancer (2016) 15:55. 10.1186/s12943-016-0539-x PubMed DOI PMC
Ahtiainen M, Wirta EV, Kuopio T, Seppälä T, Rantala J, Mecklin JP, et al. Combined Prognostic Value of CD274 (PD-L1)/PDCDI (PD-1) Expression and Immune Cell Infiltration in Colorectal Cancer as Per Mismatch Repair Status. Mod Pathol (2019) 32:866–83. 10.1038/s41379-019-0219-7 PubMed DOI
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med (2015) 372:2509–20. 10.1056/NEJMoa1500596 PubMed DOI PMC
Shen Z, Gu L, Mao D, Chen M, Jin R. Clinicopathological and Prognostic Significance of PD-L1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. World J Surg Oncol (2019) 17:4. 10.1186/s12957-018-1544-x PubMed DOI PMC
Buckowitz A, Knaebel HP, Benner A, Bläker H, Gebert J, Kienle P, et al. Microsatellite Instability in Colorectal Cancer Is Associated with Local Lymphocyte Infiltration and Low Frequency of Distant Metastases. Br J Cancer (2005) 92:1746–53. 10.1038/sj.bjc.6602534 PubMed DOI PMC
Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH, et al. Immunotherapy in Colorectal Cancer: Rationale, Challenges and Potential. Nat Rev Gastroenterol Hepatol (2019) 16:361–75. 10.1038/s41575-019-0126-x PubMed DOI PMC
Yu G, Wu Y, Wang W, Xu J, Lv X, Cao X, et al. Low-dose Decitabine Enhances the Effect of PD-1 Blockade in Colorectal Cancer with Microsatellite Stability by Re-modulating the Tumor Microenvironment. Cell Mol Immunol (2019) 16(4):401–9. 10.1038/s41423-018-0026-y PubMed DOI PMC
Venderbosch S, Nagtegaal ID, Maughan TS, Smith CG, Cheadle JP, Fisher D, et al. Mismatch Repair Status and BRAF Mutation Status in Metastatic Colorectal Cancer Patients: A Pooled Analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies. Clin Cancer Res (2014) 20:5322–30. 10.1158/1078-0432.CCR-14-0332 PubMed DOI PMC
Wherry EJ. T Cell Exhaustion. Nat Immunol (2011) 12:492–9. 10.1038/ni.2035 PubMed DOI
Zarour HM. Reversing T-Cell Dysfunction and Exhaustion in Cancer. Clin Cancer Res (2016) 22:1856–64. 10.1158/1078-0432.CCR-15-1849 PubMed DOI PMC
Yassin M, Sadowska Z, Djurhuus D, Nielsen B, Tougaard P, Olsen J, et al. Upregulation of PD-1 Follows Tumour Development in the AOM/DSS Model of Inflammation-Induced Colorectal Cancer in Mice. Immunology (2019) 158:35–46. 10.1111/imm.13093 PubMed DOI PMC
Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, et al. Human Gut Microbiome and Risk for Colorectal Cancer. J Natl Cancer Inst (2013) 105:1907–11. 10.1093/jnci/djt300 PubMed DOI PMC
Huipeng W, Lifeng G, Chuang G, Jiaying Z, Yuankun C. The Differences in Colonic Mucosal Microbiota between normal Individual and colon Cancer Patients by Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis. J Clin Gastroenterol (2014) 48:138–44. 10.1097/MCG.0b013e3182a26719 PubMed DOI
Kuwahara T, Hazama S, Suzuki N, Yoshida S, Tomochika S, Nakagami Y, et al. Intratumoural-infiltrating CD4 + and FOXP3 + T Cells as strong Positive Predictive Markers for the Prognosis of Resectable Colorectal Cancer. Br J Cancer (2019) 121:659–65. 10.1038/s41416-019-0559-6 PubMed DOI PMC
Bourgeois C, Veiga-Fernandes H, Joret AM, Rocha B, Tanchot C. CD8 Lethargy in the Absence of CD4 Help. Eur J Immunol (2002) 32:2199–207. 10.1002/1521-4141(200208)32:8<2199:AID-IMMU2199>3.0.CO;2-L PubMed DOI
Kurts C, Carbone FR, Barnden M, Blanas E, Allison J, Heath WR, et al. CD4+ T Cell Help Impairs CD8+ T Cell Deletion Induced by Cross-Presentation of Self-Antigens and Favors Autoimmunity. J Exp Med (1997) 186:2057–62. 10.1084/jem.186.12.2057 PubMed DOI PMC
Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon EK, et al. Naive Tumor-specific CD4(+) T Cells Differentiated In Vivo Eradicate Established Melanoma. J Exp Med (2010) 207:651–67. 10.1084/jem.20091921 PubMed DOI PMC
Gianchecchi E, Delfino DV, Fierabracci A. Recent Insights into the Role of the PD-1/PD-L1 Pathway in Immunological Tolerance and Autoimmunity. Autoimmun Rev (2013) 12:1091–100. 10.1016/j.autrev.2013.05.003 PubMed DOI
Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, et al. Rescue of Exhausted CD8 T Cells by PD-1-Targeted Therapies is CD28-dependent. Science (2017) 355:1423–7. 10.1126/science.aaf0683 PubMed DOI PMC
Gajewski TF, Schreiber H, Fu YX. Innate and Adaptive Immune Cells in the Tumor Microenvironment. Nat Immunol (2013) 14:1014–22. 10.1038/ni.2703 PubMed DOI PMC
Palucka AK, Coussens LM. The Basis of Oncoimmunology. Cell (2016) 164:1233–47. 10.1016/j.cell.2016.01.049 PubMed DOI PMC
Sharma P, Allison JP. The Future of Immune Checkpoint Therapy. Science (2015) 348:56–61. 10.1126/science.aaa8172 PubMed DOI
Reissfelder C, Stamova S, Gossmann C, Braun M, Bonertz A, Walliczek U, et al. Tumor-specific Cytotoxic T Lymphocyte Activity Determines Colorectal Cancer Patient Prognosis. J Clin Invest (2015) 125:739–51. 10.1172/JCI74894 PubMed DOI PMC
Kwak Y, Koh J, Kim DW, Kang SB, Kim WH, Lee HS, et al. Immunoscore Encompassing CD3+ and CD8+ T Cell Densities in Distant Metastasis is a Robust Prognostic Marker for Advanced Colorectal Cancer. Oncotarget (2016) 7:81778–90. 10.18632/oncotarget.13207 PubMed DOI PMC
Miller TJ, Anyaegbu CC, Lee-Pullen TF, Spalding LJ, Platell CF, McCoy MJ, et al. PD-L1+ Dendritic Cells in the Tumor Microenvironment Correlate with Good Prognosis and CD8+ T Cell Infiltration in colon Cancer. Cancer Sci (2021) 112:1173–83. 10.1111/cas.14781 PubMed DOI PMC
Dahlin AM, Henriksson ML, Van Guelpen B, Stenling R, Oberg A, Rutegård J, et al. Colorectal Cancer Prognosis Depends on T-Cell Infiltration and Molecular Characteristics of the Tumor. Mod Pathol (2011) 24:671–82. 10.1038/modpathol.2010.234 PubMed DOI
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, Density, and Location of Immune Cells within Human Colorectal Tumors Predict Clinical Outcome. Science (2006) 313:1960–4. 10.1126/science.1129139 PubMed DOI
Huang CY, Chiang SF, Ke TW, Chen TW, You YS, Chen WT, et al. Clinical Significance of Programmed Death 1 Ligand-1 (CD274/PD-L1) and Intra-tumoral CD8+ T-Cell Infiltration in Stage II-III Colorectal Cancer. Sci Rep (2018) 8:15658. 10.1038/s41598-018-33927-5 PubMed DOI PMC
Anfossi N, André P, Guia S, Falk CS, Roetynck S, Stewart CA, et al. Human NK Cell Education by Inhibitory Receptors for MHC Class I. Immunity (2006) 25:331–42. 10.1016/j.immuni.2006.06.013 PubMed DOI
Coppola A, Arriga R, Lauro D, Del Principe MI, Buccisano F, Maurillo L, et al. NK Cell Inflammation in the Clinical Outcome of Colorectal Carcinoma. Front Med (Lausanne) (2015) 2:33. 10.3389/fmed.2015.00033 PubMed DOI PMC
Schwartz M, Zhang Y, Rosenblatt JD. B Cell Regulation of the Anti-tumor Response and Role in Carcinogenesis. J Immunother Cancer (2016) 4:40. 10.1186/s40425-016-0145-x PubMed DOI PMC
Shimabukuro-Vornhagen A, Schlößer HA, Gryschok L, Malcher J, Wennhold K, Garcia-Marquez M, et al. Characterization of Tumor-Associated B-Cell Subsets in Patients with Colorectal Cancer. Oncotarget (2014) 5:4651–64. 10.18632/oncotarget.1701 PubMed DOI PMC
Toor SM, Sasidharan Nair V, Murshed K, Abu Nada M, Elkord E. Tumor-Infiltrating Lymphoid Cells in Colorectal Cancer Patients with Varying Disease Stages and Microsatellite Instability-High/Stable Tumors. Vaccines (Basel) (2021) 9:64. 10.3390/vaccines9010064 PubMed DOI PMC
Nirschl CJ, Drake CG. Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy. Clin Cancer Res (2013) 19:4917–24. 10.1158/1078-0432.CCR-12-1972 PubMed DOI PMC
Ren D, Hua Y, Yu B, Ye X, He Z, Li C, et al. Predictive Biomarkers and Mechanisms Underlying Resistance to PD1/PD-L1 Blockade Cancer Immunotherapy. Mol Cancer (2020) 19:19. 10.1186/s12943-020-1144-6 PubMed DOI PMC
Turvey SE, Broide DH. Innate Immunity. J Allergy Clin Immunol (2010) 125:S24–S32. 10.1016/j.jaci.2009.07.016 PubMed DOI PMC
Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated Macrophages as Major Players in the Tumor Microenvironment. Cancers (Basel) (2014) 6(3):1670–90. 10.3390/cancers6031670 PubMed DOI PMC
Sica A, Mantovani A. Macrophage Plasticity and Polarization: In Vivo Veritas. J Clin Invest (2012) 122(3):787–95. 10.1172/JCI59643 PubMed DOI PMC
Ngambenjawong C, Gustafson HH, Pun SH. Progress in Tumor-Associated Macrophage (TAM)-targeted Therapeutics. Adv Drug Deliv Rev (2017) 114:206–21. 10.1016/j.addr.2017.04.010 PubMed DOI PMC
Liu Y, Cao X. The Origin and Function of Tumor-Associated Macrophages. Cel Mol Immunol (2015) 12:1–4. 10.1038/cmi.2014.83 PubMed DOI PMC
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
Lian G, Chen S, Ouyang M, Li F, Chen L, Yang J, et al. Colon Cancer Cell Secretes EGF to Promote M2 Polarization of TAM through EGFR/PI3K/AKT/mTOR Pathway. Technol Cancer Res Treat (2019) 18:1533033819849068. 10.1177/1533033819849068 PubMed DOI PMC
Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ, et al. Transforming Growth Factor Inhibits the Antigen-Presenting Functions and Antitumor Activity of Dendritic Cell Vaccines. Cancer Res (2003) 63(8):1860–4. PubMed
Orsini G, Legitimo A, Failli A, Ferrari P, Nicolini A, Spisni R, et al. Defective Generation and Maturation of Dendritic Cells from Monocytes in Colorectal Cancer Patients during the Course of Disease. Int J Mol Sci (2013) 14(11):22022–41. 10.3390/ijms141122022 PubMed DOI PMC
Hsu YL, Chen YJ, Chang WA, Jian SF, Fan HL, Wang JY, et al. Interaction between Tumor-Associated Dendritic Cells and colon Cancer Cells Contributes to Tumor Progression via CXCL1. Int J Mol Sci (2018) 19(8):2427. 10.3390/ijms19082427 PubMed DOI PMC
Della Porta M, Danova M, Rigolin GM, Brugnatelli S, Rovati B, Tronconi C, et al. Dendritic Cells and Vascular Endothelial Growth Factor in Colorectal Cancer: Correlations with Clinicobiological Findings. Oncology (2005) 68(2-3):276–84. 10.1159/000086784 PubMed DOI
Ammendola M, Sacco R, Sammarco G, Donato G, Montemurro S, Ruggieri E, et al. Correlation between Serum Tryptase, Mast Cells Positive to Tryptase and Microvascular Density in colo-rectal Cancer Patients: Possible Biological-Clinical Significance. PLoS One (2014) 9(6):e99512. 10.1371/journal.pone.0099512 PubMed DOI PMC
Suzuki S, Ichikawa Y, Nakagawa K, Kumamoto T, Mori R, Matsuyama R, et al. High Infiltration of Mast Cells Positive to Tryptase Predicts Worse Outcome Following Resection of Colorectal Liver Metastases. BMC Cancer (2015) 15:840. 10.1186/s12885-015-1863-z PubMed DOI PMC
Zhao P, Zhou P, Tang T, Si R, Ji Y, Hu X, et al. Levels of Circulating Mast Cell Progenitors and Tumour-Infiltrating Mast Cells in Patients with Colorectal Cancer. Oncol Rep (2022) 47:89. 10.3892/or.2022.8300 PubMed DOI PMC
Sinha P, Chornoguz O, Clements VK, Artemenko KA, Zubarev RA, Ostrand-Rosenberg S, et al. Myeloid-derived Suppressor Cells Express the Death Receptor Fas and Apoptose in Response to T Cell-Expressed FasL. Blood (2011) 117(20):5381–90. 10.1182/blood-2010-11-321752 PubMed DOI PMC
Fleming V, Hu X, Weber R, Nagibin V, Groth C, Altevogt P, et al. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression. Front Immunol (2018) 9:398. 10.3389/fimmu.2018.00398 PubMed DOI PMC
Dosset M, Vargas TR, Lagrange A, Boidot R, Végran F, Roussey A, et al. PD-1/PD-L1 Pathway: An Adaptive Immune Resistance Mechanism to Immunogenic Chemotherapy in Colorectal Cancer. Oncoimmunology (2018) 7(6):e1433981. 10.1080/2162402X.2018.1433981 PubMed DOI PMC
McClellan JL, Davis JM, Steiner JL, Enos RT, Jung SH, Carson JA, et al. Linking Tumor-Associated Macrophages, Inflammation, and Intestinal Tumorigenesis: Role of MCP-1. Am J Physiol Gastrointest Liver Physiol (2012) 303(10):G1087–95. 10.1152/ajpgi.00252.2012 PubMed DOI PMC
Vermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt Activity Defines colon Cancer Stem Cells and is Regulated by the Microenvironment. Nat Cel Biol (2010) 5:468–76. 10.1038/ncb2048 PubMed DOI
Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, et al. Interaction with colon Cancer Cells Hyperactivates TGF-β Signaling in Cancer-Associated Fibroblasts. Oncogene (2014) 1:97–107. 10.1038/onc.2012.536 PubMed DOI
Vellinga TT, den Uil S, Rinkes IH, Marvin D, Ponsioen B, Alvarez-Varela A, et al. Collagen-rich Stroma in Aggressive colon Tumors Induces Mesenchymal Gene Expression and Tumor Cell Invasion. Oncogene (2016) 35:5263–71. 10.1038/onc.2016.60 PubMed DOI
Kalluri R. The Biology and Function of Fibroblasts in Cancer. Nat Rev Cancer (2016) 9:582–98. 10.1038/nrc.2016.73 PubMed DOI
Mele V, Muraro MG, Calabrese D, Pfaff D, Amatruda N, Amicarella F, et al. Mesenchymal Stromal Cells Induce Epithelial-To-Mesenchymal Transition in Human Colorectal Cancer Cells through the Expression of Surface-Bound TGF-β. Int J Cancer (2014) 11:2583–94. 10.1002/ijc.28598 PubMed DOI PMC
Brabletz T, Kalluri R, Nieto MA, Weinberg RA. EMT in Cancer. Nat Rev Cancer (2018) 18:128–34. 10.1038/nrc.2017.118 PubMed DOI
Burger GA, Danen EHJ, Beltman JB. Deciphering Epithelial-Mesenchymal Transition Regulatory Networks in Cancer through Computational Approaches. Front Oncol (2017) 7:162. 10.3389/fonc.2017.00162 PubMed DOI PMC
Jiang Y, Zhan H. Communication between EMT and PD-L1 Signaling: New Insights into Tumor Immune Evasion. Cancer Lett (2020) 468:72–81. 10.1016/j.canlet.2019.10.013 PubMed DOI
Terry S, Savagner P, Ortiz-Cuaran S, Mahjoubi L, Saintigny P, Thiery JP, et al. New Insights into the Role of EMT in Tumor Immune Escape. Mol Oncol (2017) 11:824–46. 10.1002/1878-0261.12093 PubMed DOI PMC
Zhan HX, Zhou B, Cheng YG, Xu JW, Wang L, Zhang GY, et al. Crosstalk between Stromal Cells and Cancer Cells in Pancreatic Cancer: New Insights into Stromal Biology. Cancer Lett (2017) 392:83–93. 10.1016/j.canlet.2017.01.041 PubMed DOI
Ma HY, Liu XZ, Liang CM. Inflammatory Microenvironment Contributes to Epithelial-Mesenchymal Transition in Gastric Cancer. World J Gastroenterol (2016) 22:6619–28. 10.3748/wjg.v22.i29.6619 PubMed DOI PMC
Zippi M, De Toma G, Minervini G, Cassieri C, Pica R, Colarusso D, et al. Desmoplasia Influenced Recurrence of Disease and Mortality in Stage III Colorectal Cancer within Five Years after Surgery and Adjuvant Therapy. Saudi J Gastroenterol (2017) 23:39–44. 10.4103/1319-3767.199114 PubMed DOI PMC
Ueno H, Shinto E, Shimazaki H, Kajiwara Y, Sueyama T, Yamamoto J, et al. Histologic Categorization of Desmoplastic Reaction: Its Relevance to the Colorectal Cancer Microenvironment and Prognosis. Ann Surg Oncol (2015) 22:1504–12. 10.1245/s10434-014-4149-9 PubMed DOI
Sueyama T, Kajiwara Y, Mochizuki S, Shimazaki H, Shinto E, Hase K, et al. Periostin as a Key Molecule Defining Desmoplastic Environment in Colorectal Cancer. Virchows Arch (2021) 478:865–74. 10.1007/s00428-020-02965-8 PubMed DOI
Becht E, de Reyniès A, Giraldo NA, Pilati C, Buttard B, Lacroix L, et al. Immune and Stromal Classification of Colorectal Cancer is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy. Clin Cancer Res (2016) 22(16):4057–66. 10.1158/1078-0432.CCR-15-2879 PubMed DOI
Tougeron D, Fauquembergue E, Rouquette A, Le Pessot F, Sesboüé R, Laurent M, et al. Tumor-infiltrating Lymphocytes in Colorectal Cancers with Microsatellite Instability are Correlated with the Number and Spectrum of Frameshift Mutations. Mod Pathol (2009) 22(9):1186–95. 10.1038/modpathol.2009.80 PubMed DOI
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med (2010) 363(8):711–23. 10.1056/NEJMoa1003466 PubMed DOI PMC
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. N Engl J Med (2012) 366(26):2443–54. 10.1056/NEJMoa1200690 PubMed DOI PMC
Fan J, Shang D, Han B, Song J, Chen H, Yang JM, et al. Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer? Theranostics (2018) 8:5784–800. 10.7150/thno.29035 PubMed DOI PMC
Beak JH, Kim KJ. Expansion of Tumor-Infiltrating Lymphocytes and Their Potential for Application to Adoptive Cell Therapy in Patients with Colorectal Cancer. Eur J Surg Oncol (2019) 45(2):e58–9. 10.1016/j.ejso.2018.10.223 DOI
Koelzer VH, Lugli A, Dawson H, Hädrich M, Berger MD, Borner M, et al. CD8/CD45RO T-Cell Infiltration in Endoscopic Biopsies of Colorectal Cancer Predicts Nodal Metastasis and Survival. J Transl Med (2014) 12:81. 10.1186/1479-5876-12-81 PubMed DOI PMC
Morris M, Platell C, Iacopetta B. Tumor-infiltrating Lymphocytes and Perforation in colon Cancer Predict Positive Response to 5-fluorouracil Chemotherapy. Clin Cancer Res (2008) 14(5):1413–7. 10.1158/1078-0432.CCR-07-1994 PubMed DOI
Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, et al. Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases are Prognostic for Response to Chemotherapy. Cancer Res (2011) 71(17):5670–7. 10.1158/0008-5472.CAN-11-0268 PubMed DOI
Valenzuela G, Canepa J, Simonetti C, Solo de Zaldívar L, Marcelain K, González-Montero J, et al. Consensus Molecular Subtypes of Colorectal Cancer in Clinical Practice: A Translational Approach. World J Clin Oncol (2021) 12(11):1000–8. 10.5306/wjco.v12.i11.1000 PubMed DOI PMC
Eide PW, Moosavi SH, Eilertsen IA, Brunsell TH, Langerud J, Berg KCG, et al. Metastatic Heterogeneity of the Consensus Molecular Subtypes of Colorectal Cancer. NPJ Genom Med (2021) 6:59. 10.1038/s41525-021-00223-7 PubMed DOI PMC
Fontana E, Eason K, Cervantes A, Salazar R, Sadanandam A. Context Matters-Consensus Molecular Subtypes of Colorectal Cancer as Biomarkers for Clinical Trials. Ann Oncol (2019) 30(4):520–7. 10.1093/annonc/mdz052 PubMed DOI PMC
Kamal Y, Schmit SL, Hoehn HJ, Amos CI, Frost HR. Transcriptomic Differences between Primary Colorectal Adenocarcinomas and Distant Metastases Reveal Metastatic Colorectal Cancer Subtypes. Cancer Res (2019) 79:4227–41. 10.1158/0008-5472.CAN-18-3945 PubMed DOI PMC
Akishima-Fukasawa Y, Ino Y, Nakanishi Y, Miura A, Moriya Y, Kondo T, et al. Significance of PGP9.5 Expression in Cancer-Associated Fibroblasts for Prognosis of Colorectal Carcinoma. Am J Clin Pathol (2010) 134:71–9. 10.1309/AJCPRJP39MIDSGBH PubMed DOI
Glentis A, Oertle P, Mariani P, Chikina A, El Marjou F, Attieh Y, et al. Cancer-associated Fibroblasts Induce Metalloprotease-independent Cancer Cell Invasion of the Basement Membrane. Nat Commun (2017) 8:924. 10.1038/s41467-017-00985-8 PubMed DOI PMC
Ren J, Ding L, Zhang D, Shi G, Xu Q, Shen S, et al. Carcinoma-associated Fibroblasts Promote the Stemness and Chemoresistance of Colorectal Cancer by Transferring Exosomal lncRNA H19. Theranostics (2018) 8(14):3932–48. 10.7150/thno.25541 PubMed DOI PMC
Zhang R, Qi F, Shao S, Li G, Feng Y. Human Colorectal Cancer-Derived Carcinoma Associated Fibroblasts Promote CD44-Mediated Adhesion of Colorectal Cancer Cells to Endothelial Cells by Secretion of HGF. Cancer Cel Int (2019) 19:192. 10.1186/s12935-019-0914-y PubMed DOI PMC
Miyazaki K, Togo S, Okamoto R, Idiris A, Kumagai H, Miyagi Y, et al. Collective Cancer Cell Invasion in Contact with Fibroblasts through Integrin-α5β1/fibronectin Interaction in Collagen Matrix. Cancer Sci (2020) 111:4381–92. 10.1111/cas.14664 PubMed DOI PMC
Unterleuthner D, Neuhold P, Schwarz K, Janker L, Neuditschko B, Nivarthi H, et al. Cancer-associated Fibroblast-Derived WNT2 Increases Tumor Angiogenesis in Colon Cancer. Angiogenesis (2020) 23:159–77. 10.1007/s10456-019-09688-8 PubMed DOI PMC
Bauer K, Michel S, Reuschenbach M, Nelius N, von Knebel Doeberitz M, Kloor M, et al. Dendritic Cell and Macrophage Infiltration in Microsatellite-Unstable and Microsatellite -stable Colorectal Cancer. Fam Cancer (2011) 10:557–65. 10.1007/s10689-011-9449-7 PubMed DOI
Gulubova MV, Ananiev JR, Vlaykova TI, Yovchev Y, Tsoneva V, Manolova IM, et al. Role of Dendritic Cells in Progression and Clinical Outcome of colon Cancer. Int J Colorectal Dis (2012) 27:159–69. 10.1007/s00384-011-1334-1 PubMed DOI
Hu Z, Ma Y, Shang Z, Hu S, Liang K, Liang W, et al. Improving Immunotherapy for Colorectal Cancer Using Dendritic Cells Combined with Anti-programmed Death-Ligand In Vitro . Oncol Lett (2018) 15:5345–51. 10.3892/ol.2018.7978 PubMed DOI PMC
Berntsson J, Nodin B, Eberhard J, Micke P, Jirström K. Prognostic Impact of Tumour-Infiltrating B Cells and Plasma Cells in Colorectal Cancer. Int J Cancer (2016) 139:1129–39. 10.1002/ijc.30138 PubMed DOI
Edin S, Kaprio T, Hagström J, Larsson P, Mustonen H, Böckelman C, et al. The Prognostic Importance of CD20+ B Lymphocytes in Colorectal Cancer and the Relation to Other Immune Cell Subsets. Sci Rep (2019) 9:19997. 10.1038/s41598-019-56441-8 PubMed DOI PMC
Mullins CS, Gock M, Krohn M, Linnebacher M. Human Colorectal Carcinoma Infiltrating B Lymphocytes are Active Secretors of the Immunoglobulin Isotypes A, G, and M. Cancers (Basel) (2019) 11:776. 10.3390/cancers11060776 PubMed DOI PMC
Berntsson J, Svensson MC, Leandersson K, Nodin B, Micke P, Larsson AH, et al. The Clinical Impact of Tumour-Infiltrating Lymphocytes in Colorectal Cancer Differs by Anatomical Subsite: A Cohort Study. Int J Cancer (2017) 141:1654–66. 10.1002/ijc.30869 PubMed DOI PMC
Digiacomo N, Bolzacchini E, Veronesi G, Cerutti R, Sahnane N, Pinotti G, et al. Neuroendocrine Differentiation, Microsatellite Instability, and Tumor-Infiltrating Lymphocytes in Advanced Colorectal Cancer with BRAF Mutation. Clin Colorectal Cancer (2019) 18(2):e251–60. 10.1016/j.clcc.2018.12.003 PubMed DOI
Glaire MA, Domingo E, Sveen A, Bruun J, Nesbakken A, Nicholson G, et al. Tumour-infiltrating CD8+ Lymphocytes and Colorectal Cancer Recurrence by Tumour and Nodal Stage. Br J Cancer (2019) 121:474–82. 10.1038/s41416-019-0540-4 PubMed DOI PMC
Craig SG, Humphries MP, Alderdice M, Bingham V, Richman SD, Loughrey MB, et al. Immune Status Is Prognostic for Poor Survival in Colorectal Cancer Patients and is Associated with Tumour Hypoxia. Br J Cancer (2020) 123:1280–8. 10.1038/s41416-020-0985-5 PubMed DOI PMC
Hartman DJ, Frank M, Seigh L, Choudry H, Pingpank J, Holtzman M, et al. Automated Quantitation of CD8-Positive T Cells Predicts Prognosis in Colonic Adenocarcinoma with Mucinous, Signet Ring Cell, or Medullary Differentiation Independent of Mismatch Repair Protein Status. Am J Surg Pathol (2020) 44:991–1001. 10.1097/PAS.0000000000001468 PubMed DOI PMC
Fuchs TL, Sioson L, Sheen A, Jafari-Nejad K, Renaud CJ, Andrici J, et al. Assessment of Tumor-Infiltrating Lymphocytes Using International TILs Working Group (ITWG) System is a Strong Predictor of Overall Survival in Colorectal Carcinoma: A Study of 1034 Patients. Am J Surg Pathol (2020) 44:536–44. 10.1097/PAS.0000000000001409 PubMed DOI
Lalos A, Tülek A, Tosti N, Mechera R, Wilhelm A, Soysal S, et al. Prognostic Significance of CD8+ T-Cells Density in Stage III Colorectal Cancer Depends Od SDF-1 Expression. Sci Rep (2021) 11:775. 10.1038/s41598-020-80382-2 PubMed DOI PMC
Al-Badran SS, Grant L, Campo MV, Inthagard J, Pennel K, Quinn J, et al. Relationship between Immune Checkpoint Proteins, Tumour Microenvironment Characteristics, and Prognosis in Primary Operable Colorectal Cancer. J Pathol Clin Res (2021) 7:121–34. 10.1002/cjp2.193 PubMed DOI PMC