From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer

. 2018 Dec 20 ; 20 (1) : . [epub] 20181220

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid30577521

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.

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Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. PubMed DOI

Matzenauer M., Vrána D., Vlachová Z., Aujesky R., Vrba R., Neoral C., Melichar B. Stereotactic radiotherapy in the treatment of local recurrences of esophageal cancer. Oncol. Lett. 2017;13:1807–1810. doi: 10.3892/ol.2017.5605. PubMed DOI PMC

Vrana D., Matzenauer M., Aujesky R., Vrba R., Neoral C., Melichar B., Souček P. Potential Predictive Role of MicroRNAs in the Neoadjuvant Treatment of Esophageal Cancer. Anticancer Res. 2017;37:403–412. doi: 10.21873/anticanres.11332. PubMed DOI

Vrana D., Hlavac V., Brynychova V., Vaclavikova R., Neoral C., Vrba J., Aujesky R., Matzenauer M., Melichar B., Soucek P. ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer. Int. J. Mol. Sci. 2018;19:868. doi: 10.3390/ijms19030868. PubMed DOI PMC

Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. PubMed DOI

Marconcini R., Spagnolo F., Stucci L.S., Ribero S., Marra E., Rosa F., Picasso V., Di Guardo L., Cimminiello C., Cavalieri S., et al. Current status and perspectives in immunotherapy for metastatic melanoma. Oncotarget. 2018;9:12452–12470. doi: 10.18632/oncotarget.23746. PubMed DOI PMC

Santoni M., Massari F., Di Nunno V., Conti A., Cimadamore A., Scarpelli M., Montironi R., Cheng L., Battelli N., Lopez-Beltran A. Immunotherapy in renal cell carcinoma: Latest evidence and clinical implications. Drugs Context. 2018;7:212528. doi: 10.7573/dic.212528. PubMed DOI PMC

Cancer Genome Atlas Research Network Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–175. doi: 10.1038/nature20805. PubMed DOI PMC

Secrier M., Li X., de Silva N., Eldridge M.D., Contino G., Bornschein J., MacRae S., Grehan N., O’Donovan M., Miremadi A., et al. Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nat. Genet. 2016;48:1131–1141. doi: 10.1038/ng.3659. PubMed DOI PMC

Cancer Genome Atlas Research Network Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209. doi: 10.1038/nature13480. PubMed DOI PMC

Alsaab H.O., Sau S., Alzhrani R., Tatiparti K., Bhise K., Kashaw S.K., Iyer A.K. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front. Pharmacol. 2017;8:561. doi: 10.3389/fphar.2017.00561. PubMed DOI PMC

Böger C., Behrens H.M., Mathiak M., Krüger S., Kalthoff H., Röcken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016;7:24269–24283. doi: 10.18632/oncotarget.8169. PubMed DOI PMC

Pereira M.A., Ramos M.F.K.P., Faraj S.F., Dias A.R., Yagi O.K., Zilberstein B., Cecconello I., Alves V.A.F., de Mello E.S., Ribeiro U., Jr. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J. Surg. Oncol. 2018;117:829–839. doi: 10.1002/jso.25022. PubMed DOI

Tamura T., Ohira M., Tanaka H., Muguruma K., Toyokawa T., Kubo N., Sakurai K., Amano R., Kimura K., Shibutani M., et al. Programmed Death-1 Ligand-1 (PDL1) Expression Is Associated with the Prognosis of Patients with Stage II/III Gastric Cancer. Anticancer Res. 2015;35:5369–5376. PubMed

Zhang L., Qiu M., Jin Y., Ji J., Li B., Wang X., Yan S., Xu R., Yang D. Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors. Int. J. Clin. Exp. Pathol. 2015;8:11084–11091. PubMed PMC

Eto S., Yoshikawa K. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2016;19:466–471. doi: 10.1007/s10120-015-0519-7. PubMed DOI

Tsutsumi S., Saeki H., Nakashima Y., Ito S., Oki E., Morita M., Oda Y., Okano S., Maehara Y. Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Sci. 2017;108:1119–1127. doi: 10.1111/cas.13237. PubMed DOI PMC

Kim R., Keam B., Kwon D., Ock C.Y., Kim M., Kim T.M., Kim H.J., Jeon Y.K., Park I.K., Kang C.H., et al. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma. World J. Gastroenterol. 2016;22:8389–8397. doi: 10.3748/wjg.v22.i37.8389. PubMed DOI PMC

Zhang W., Pang Q., Zhang X., Yan C., Wang Q., Yang J., Yu S., Liu X., Pan Y., Yuan Z., et al. Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor. Cancer Sci. 2017;108:590–597. doi: 10.1111/cas.13197. PubMed DOI PMC

Zhu Y., Li M., Mu D., Kong L., Zhang J., Zhao F., Li Z., Liu X., Bo C., Yu J. CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer. Oncotarget. 2016;7:71455–71465. doi: 10.18632/oncotarget.12213. PubMed DOI PMC

Jiang Y., Lo A.W.I., Wong A., Chen W., Wang Y., Lin L., Xu J. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget. 2017;8:30175–30189. doi: 10.18632/oncotarget.15621. PubMed DOI PMC

Jesinghaus M., Steiger K., Slotta-Huspenina J., Drecoll E., Pfarr N., Meyer P., Konukiewitz B., Bettstetter M., Wieczorek K., Ott K., et al. Increased intraepithelial CD3+ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping. Oncotarget. 2017;8:46756–46768. doi: 10.18632/oncotarget.18606. PubMed DOI PMC

Chen M.F., Chen P.T., Chen W.C., Lu M.S., Lin P.Y., Lee KD. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget. 2016;7:7913–7924. doi: 10.18632/oncotarget.6861. PubMed DOI PMC

Kawazoe A., Kuwata T., Kuboki Y., Shitara K., Nagatsuma A.K., Aizawa M., Yoshino T., Doi T., Ohtsu A., Ochiai A. Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer. 2017;20:407–415. doi: 10.1007/s10120-016-0631-3. PubMed DOI

Thompson E.D., Zahurak M., Murphy A., Cornish T., Cuka N., Abdelfatah E., Yang S., Duncan M., Ahuja N., Taube J.M., et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017;66:794–801. doi: 10.1136/gutjnl-2015-310839. PubMed DOI PMC

Yang J.H., Kim H., Roh S.Y., Lee M.A., Park J.M., Lee H.H., Park C.H., Lee H.H., Jung E.S., Lee S.H., et al. Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer. Gastric Cancer. 2018:1–8. doi: 10.1007/s10120-018-0842-x. PubMed DOI

Seo A.N., Kang B.W., Kwon O.K., Park K.B., Lee S.S., Chung H.Y., Yu W., Bae H.I., Jeon S.W., Kang H., et al. Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer. Br. J. Cancer. 2017;117:1753–1760. doi: 10.1038/bjc.2017.369. PubMed DOI PMC

Ito S., Okano S., Morita M., Saeki H., Tsutsumi S., Tsukihara H., Nakashima Y., Ando K., Imamura Y., Ohgaki K., et al. Expression of PD-L1 and HLA Class I in Esophageal Squamous Cell Carcinoma: Prognostic Factors for Patient Outcome. Ann. Surg. Oncol. 2016;23(Suppl. S4):508–515. doi: 10.1245/s10434-016-5376-z. PubMed DOI

Hsieh C.C., Hsu H.S., Li A.F., Chen Y.J. Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma. J. Thorac. Dis. 2018;10:4433–4444. doi: 10.21037/jtd.2018.06.167. PubMed DOI PMC

Kollmann D., Ignatova D., Jedamzik J., Chang Y.T., Jomrich G., Baierl A., Kazakov D., Michal M., French L.E., Hoetzenecker W., et al. PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma. Oncoimmunology. 2018;7:e1435226. doi: 10.1080/2162402X.2018.1435226. PubMed DOI PMC

Tanaka K., Miyata H., Sugimura K., Kanemura T., Hamada-Uematsu M., Mizote Y., Yamasaki M., Wada H., Nakajima K., Takiguchi S., et al. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy. Cancer Sci. 2016;107:726–733. doi: 10.1111/cas.12938. PubMed DOI PMC

Li Z., Lai Y., Sun L., Zhang X., Liu R., Feng G., Zhou L., Jia L., Huang X., Kang Q., et al. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. Hum. Pathol. 2016;55:182–189. doi: 10.1016/j.humpath.2016.05.012. PubMed DOI

Wang L., Zhang Q., Ni S., Tan C., Cai X., Huang D., Sheng W. Programmed death-ligand 1 expression in gastric cancer: Correlation with mismatch repair deficiency and HER2-negative status. Cancer Med. 2018;7:2612–2620. doi: 10.1002/cam4.1502. PubMed DOI PMC

Saito R., Abe H., Kunita A., Yamashita H., Seto Y., Fukayama M. Overexpression and gene amplification of PD-L1 in cancer cells and PD-L1+ immune cells in Epstein-Barr virus-associated gastric cancer: The prognostic implications. Mod. Pathol. 2017;30:427–439. doi: 10.1038/modpathol.2016.202. PubMed DOI

Cho J., Lee J., Bang H., Kim S.T., Park S.H., An J.Y., Choi M.G., Lee J.H., Sohn T.S., Bae J.M., et al. cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability. Oncotarget. 2017;8:13320–13328. doi: 10.18632/oncotarget.14519. PubMed DOI PMC

Ma C., Patel K., Singhi A.D., Ren B., Zhu B., Shaikh F., Sun W. Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated with Epstein-Barr Virus or Microsatellite Instability. Am. J. Surg. Pathol. 2016;40:1496–1506. doi: 10.1097/PAS.0000000000000698. PubMed DOI

Koh J., Ock C.Y., Kim J.W., Nam S.K., Kwak Y., Yun S., Ahn S.H., Park D.J., Kim H.H., Kim W.H., et al. Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients. Oncotarget. 2017;8:26356–26367. doi: 10.18632/oncotarget.15465. PubMed DOI PMC

An Investigational Immuno-therapy Study of Nivolumab or Placebo in Patients With Resected Esophageal or Gastroesophageal Junction Cancer (CheckMate 577) [(accessed on 13 November 2018)]; Available online: https://clinicaltrials.gov/ct2/show/NCT02743494.

Antonia S.J., Villegas A., Daniel D., Vicente D., Murakami S., Hui R., Kurata T., Chiappori A., Lee K.H., de Wit M., et al. PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N. Engl. J. Med. 2018;379:2342–2350. doi: 10.1056/NEJMoa1809697. PubMed DOI

Tang Y., Li G., Wu S., Tang L., Zhang N., Liu J., Zhang S., Yao L. Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers. Oncol. Lett. 2018;15:4988–4996. doi: 10.3892/ol.2018.7984. PubMed DOI PMC

Minsky B.D., Pajak T.F., Ginsberg R.J., Pisansky T.M., Martenson J., Komaki R., Okawara G., Rosenthal S.A., Kelsen D.P. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: High-dose versus standard-dose radiation therapy. J. Clin. Oncol. 2002;20:1167–1174. doi: 10.1200/JCO.2002.20.5.1167. PubMed DOI

Dovedi S.J., Adlard A.L., Lipowska-Bhalla G., McKenna C., Jones S., Cheadle E.J., Stratford I.J., Poon E., Morrow M., Stewart R., et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–5468. doi: 10.1158/0008-5472.CAN-14-1258. PubMed DOI

Mimura K., Teh J.L., Okayama H., Shiraishi K., Kua L.F., Koh V., Smoot D.T., Ashktorab H., Oike T., Suzuki Y., et al. PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer. Cancer Sci. 2018;109:43–53. doi: 10.1111/cas.13424. PubMed DOI PMC

Ghebeh H., Lehe C., Barhoush E., Al-Romaih K., Tulbah A., Al-Alwan M., Hendrayani S.F., Manogaran P., Alaiya A., Al-Tweigeri T., et al. Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: Role of B7-H1 as an anti-apoptotic molecule. Breast Cancer Res. 2010;12:R48. doi: 10.1186/bcr2605. PubMed DOI PMC

Rom-Jurek E.M., Kirchhammer N., Ugocsai P., Ortmann O., Wege A.K., Brockhoff G. Regulation of Programmed Death Ligand 1 (PD-L1) Expression in Breast Cancer Cell Lines In Vitro and in Immunodeficient and Humanized Tumor Mice. Int. J. Mol. Sci. 2018;19:563. doi: 10.3390/ijms19020563. PubMed DOI PMC

Min Z., Yibo F., Xiaofang C., Kezuo H., Xiujuan Q. 5-Fluorouracil induced up-regulation of exosomal PD-L1 causing immunosuppression in gastric cancer patients. Ann. Oncol. 2018;29 doi: 10.1093/annonc/mdy268.043. DOI

Fang W., Zhang J., Hong S., Zhan J., Chen N., Qin T., Tang Y., Zhang Y., Kang S., Zhou T., et al. EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget. 2014;5:12189–12202. doi: 10.18632/oncotarget.2608. PubMed DOI PMC

Kim J.H., Park H.E., Cho N.Y., Lee H.S., Kang G.H. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br. J. Cancer. 2016;115:490–496. doi: 10.1038/bjc.2016.211. PubMed DOI PMC

Chen L., Xiong Y., Li J., Zheng X., Zhou Q., Turner A., Wu C., Lu B., Jiang J. PD-L1 Expression Promotes Epithelial to Mesenchymal Transition in Human Esophageal Cancer. Cell Physiol. Biochem. 2017;42:2267–2280. doi: 10.1159/000480000. PubMed DOI

Ng H.Y., Li J., Tao L., Lam A.K., Chan K.W., Ko J.M.Y., Yu V.Z., Wong M., Li B., Lung M.L. Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation. Transl. Oncol. 2018;11:1323–1333. doi: 10.1016/j.tranon.2018.08.005. PubMed DOI PMC

Chen K., Cheng G., Zhang F., Zhang N., Li D., Jin J., Wu J., Ying L., Mao W., Su D. Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget. 2016;7:30772–30780. doi: 10.18632/oncotarget.8956. PubMed DOI PMC

Wu Y., Cao D., Qu L., Cao X., Jia Z., Zhao T., Wang Q., Jiang J. PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer. Oncotarget. 2017;8:64066–64082. doi: 10.18632/oncotarget.19318. PubMed DOI PMC

Vanderwalde A., Spetzler D., Xiao N., Gatalica Z., Marshall J. Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med. 2018;7:746–756. doi: 10.1002/cam4.1372. PubMed DOI PMC

Kim K.J., Lee K.S., Cho H.J., Kim Y.H., Yang H.K., Kim W.H., Kang G.H. Prognostic implications of tumor-infiltrating FoxP3+ regulatory T cells and CD8+ cytotoxic T cells in microsatellite-unstable gastric cancers. Hum. Pathol. 2014;45:285–293. doi: 10.1016/j.humpath.2013.09.004. PubMed DOI

Boissière-Michot F., Lazennec G., Frugier H., Jarlier M., Roca L., Duffour J., Du Paty E., Laune D., Blanchard F., Le Pessot F., et al. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer. Oncoimmunology. 2014;3:e29256. doi: 10.4161/onci.29256. PubMed DOI PMC

Polom K., Böger C., Smyth E., Marrelli D., Behrens H.M., Marano L., Becker T., Lordick F., Röcken C., Roviello F. Synchronous metastatic gastric cancer-molecular background and clinical implications with special attention to mismatch repair deficiency. Eur. J. Surg. Oncol. 2018;44:626–631. doi: 10.1016/j.ejso.2018.02.208. PubMed DOI

Corso G., Pedrazzani C., Marrelli D., Pascale V., Pinto E., Roviello F. Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma. Arch. Surg. 2009;144:722–727. doi: 10.1001/archsurg.2009.42. PubMed DOI

Muzeau F., Fléjou J.F., Belghiti J., Thomas G., Hamelin R. Infrequent microsatellite instability in oesophageal cancers. Br. J. Cancer. 1997;75:1336–1339. doi: 10.1038/bjc.1997.226. PubMed DOI PMC

Smyth E.C., Wotherspoon A., Peckitt C., Gonzalez D., Hulkki-Wilson S., Eltahir Z., Fassan M., Rugge M., Valeri N., Okines A., et al. Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial. JAMA Oncol. 2017;3:1197–1203. doi: 10.1001/jamaoncol.2016.6762. PubMed DOI PMC

Pembrolizumab in MSI-H or dMMR Solid Tumors: ‘First Tissue/Site-Agnostic’ Approval by FDA. [(accessed on 13 November 2018)]; Available online: http://www.ascopost.com/issues/february-10-2018/pembrolizumab-in-msi-h-or-dmmr-solid-tumors-first-tissuesite-agnostic-approval-by-fda/

Kim H., An J.Y., Noh S.H., Shin S.K., Lee Y.C., Kim H. High microsatellite instability predicts good prognosis in intestinal-type gastric cancers. J. Gastroenterol. Hepatol. 2011;26:585–592. doi: 10.1111/j.1440-1746.2010.06487.x. PubMed DOI

An J.Y., Kim H., Cheong J.H., Hyung W.J., Kim H., Noh S.H. Microsatellite instability in sporadic gastric cancer: Its prognostic role and guidance for 5-FU based chemotherapy after R0 resection. Int. J. Cancer. 2012;131:505–511. doi: 10.1002/ijc.26399. PubMed DOI

Fang W.L., Chang S.C., Lan Y.T., Huang K.H., Chen J.H., Lo S.S., Hsieh M.C., Li A.F., Wu C.W., Chiou S.H. Microsatellite instability is associated with a better prognosis for gastric cancer patients after curative surgery. World J. Surg. 2012;36:2131–2138. doi: 10.1007/s00268-012-1652-7. PubMed DOI

Beghelli S., de Manzoni G., Barbi S., Tomezzoli A., Roviello F., Di Gregorio C., Vindigni C., Bortesi L., Parisi A., Saragoni L., et al. Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery. 2006;139:347–356. doi: 10.1016/j.surg.2005.08.021. PubMed DOI

Kim S.Y., Choi Y.Y., An J.Y., Shin H.B., Jo A., Choi H., Seo S.H., Bang H.J., Cheong J.H., Hyung W.J., et al. The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses. Int. J. Cancer. 2015;137:819–825. doi: 10.1002/ijc.29449. PubMed DOI

Giampieri R., Maccaroni E., Mandolesi A., Del Prete M., Andrikou K., Faloppi L., Bittoni A., Bianconi M., Scarpelli M., Bracci R., et al. Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy. Gastric Cancer. 2017;20:156–163. doi: 10.1007/s10120-016-0594-4. PubMed DOI

Oki E., Kakeji Y., Zhao Y., Yoshida R., Ando K., Masuda T., Ohgaki K., Morita M., Maehara Y. Chemosensitivity and survival in gastric cancer patients with microsatellite instability. Ann. Surg. Oncol. 2009;16:2510–2515. doi: 10.1245/s10434-009-0580-8. PubMed DOI

Falchetti M., Saieva C., Lupi R., Masala G., Rizzolo P., Zanna I., Ceccarelli K., Sera F., Mariani-Costantini R., Nesi G., et al. Gastric cancer with high-level microsatellite instability: Target gene mutations, clinicopathologic features, and long-term survival. Hum Pathol. 2008;39:925–932. doi: 10.1016/j.humpath.2007.10.024. PubMed DOI

Marrelli D., Polom K., Pascale V., Vindigni C., Piagnerelli R., De Franco L., Ferrara F., Roviello G., Garosi L., Petrioli R., et al. Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer. Ann. Surg. Oncol. 2016;23:943–950. doi: 10.1245/s10434-015-4931-3. PubMed DOI

Muro K., Chung H.C., Shankaran V., Geva R., Catenacci D., Gupta S., Eder J.P., Golan T., Le D.T., Burtness B., et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17:717–726. doi: 10.1016/S1470-2045(16)00175-3. PubMed DOI

Fuchs C.S., Doi T., Jang R.W., Muro K., Satoh T., Machado M., Sun W., Jalal S.I., Shah M.A., Metges J.P., et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients with Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018;4:e180013. doi: 10.1001/jamaoncol.2018.0013. PubMed DOI PMC

Shitara K., Özgüroğlu M., Bang Y.J., Di Bartolomeo M., Mandalà M., Ryu M.H., Fornaro L., Olesiński T., Caglevic C., Chung H.C., et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392:123–133. doi: 10.1016/S0140-6736(18)31257-1. PubMed DOI

Kang Y.K., Boku N., Satoh T., Ryu M.H., Chao Y., Kato K., Chung H.C., Chen J.S., Muro K., Kang W.K., et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–2471. doi: 10.1016/S0140-6736(17)31827-5. PubMed DOI

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