Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 6/2020

25.02.2020 | Original Article

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications

verfasst von: Yu-Jie Zhou, Gui-Qi Zhu, Xiao-Fan Lu, Kenneth I. Zheng, Qi-Wen Wang, Jin-Nan Chen, Qing-Wei Zhang, Fang-Rong Yan, Xiao-Bo Li

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy.

Methods

A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validation of immunogenomic classification was performed across six microarray datasets of 1406 samples.

Results

We found approximately half of gastric cancer samples to have higher immune cell infiltrates, PD-L1 expression, markers of cytolytic activity, and fewer copy number aberrations (all P < 0.05). We termed this group of tumours the Immune Class, which incorporated two components, namely Immune Activation and Immunosuppressive Subtype, according to immunosuppressive or activated microenvironment. Immune Activation Subtype was associated with improved survival in multivariate survival analysis and shared similar genomic characteristics with responders of anti-PD-1 therapy. Immunosuppressive Subtype featured high immune infiltration, stromal enrichment, and transforming growth factor (TGF)-β signalling pathway activation and correlated with non-responsiveness signature of checkpoint blockade therapy, which might be suitable for anti-PD-L1 and anti-TGF-β combined therapy.

Conclusions

We proposed and independently validated three reproducible immune molecular subtypes of gastric cancer, which may provide implications for patient selection of immunotherapy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzen F, Noh SH (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet (London, England) 379(9813):315–321. https://doi.org/10.1016/s0140-6736(11)61873-4 CrossRef Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzen F, Noh SH (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet (London, England) 379(9813):315–321. https://​doi.​org/​10.​1016/​s0140-6736(11)61873-4 CrossRef
4.
Zurück zum Zitat Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentral Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://​doi.​org/​10.​1056/​NEJMoa1504030 CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT (2017) 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 (London, England) 390(10111):2461–2471. https://doi.org/10.1016/s0140-6736(17)31827-5 CrossRef Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT (2017) 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 (London, England) 390(10111):2461–2471. https://​doi.​org/​10.​1016/​s0140-6736(17)31827-5 CrossRef
6.
Zurück zum Zitat Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) 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 4(5):e180013. https://doi.org/10.1001/jamaoncol.2018.0013 CrossRefPubMedPubMedCentral Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH (2018) 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 4(5):e180013. https://​doi.​org/​10.​1001/​jamaoncol.​2018.​0013 CrossRefPubMedPubMedCentral
7.
9.
Zurück zum Zitat Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, Ziv E, Culhane AC, Paull EO, Sivakumar IKA, Gentles AJ, Malhotra R, Farshidfar F, Colaprico A, Parker JS, Mose LE, Voni NS, Liu J, Liu Y, Rader J, Dhankani V, Reynolds SM, Bowlby R, Califano A, Cherniack AD, Anastassiou D, Bedognetti D, Rao A, Chen K, Krasnitz A, Hu H, Malta TM, Noushmehr H, Pedamallu CS, Bullman S, Ojesina AI, Lamb A, Zhou W, Shen H, Choueiri TK, Weinstein JN, Guinney J, Saltz J, Holt RA, Rabkin CE, Cancer Genome Atlas Research N, Lazar AJ, Serody JS, Demicco EG, Disis ML, Vincent BG, Shmulevich L (2018) The Immune Landscape of Cancer. Immunity 48(4):812–830 e814. https://doi.org/10.1016/j.immuni.2018.03.023 CrossRefPubMedPubMedCentral Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, Ziv E, Culhane AC, Paull EO, Sivakumar IKA, Gentles AJ, Malhotra R, Farshidfar F, Colaprico A, Parker JS, Mose LE, Voni NS, Liu J, Liu Y, Rader J, Dhankani V, Reynolds SM, Bowlby R, Califano A, Cherniack AD, Anastassiou D, Bedognetti D, Rao A, Chen K, Krasnitz A, Hu H, Malta TM, Noushmehr H, Pedamallu CS, Bullman S, Ojesina AI, Lamb A, Zhou W, Shen H, Choueiri TK, Weinstein JN, Guinney J, Saltz J, Holt RA, Rabkin CE, Cancer Genome Atlas Research N, Lazar AJ, Serody JS, Demicco EG, Disis ML, Vincent BG, Shmulevich L (2018) The Immune Landscape of Cancer. Immunity 48(4):812–830 e814. https://​doi.​org/​10.​1016/​j.​immuni.​2018.​03.​023 CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, Castro de Moura M, Putra J, Camprecios G, Bassaganyas L, Akers N, Losic B, Waxman S, Thung SN, Mazzaferro V, Esteller M, Friedman SL, Schwartz M, Villanueva A, Llovet JM (2017) Identification of an immune-specific class of hepatocellular carcinoma based on molecular features. Gastroenterology 153(3):812–826. https://doi.org/10.1053/j.gastro.2017.06.007 CrossRefPubMed Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, Castro de Moura M, Putra J, Camprecios G, Bassaganyas L, Akers N, Losic B, Waxman S, Thung SN, Mazzaferro V, Esteller M, Friedman SL, Schwartz M, Villanueva A, Llovet JM (2017) Identification of an immune-specific class of hepatocellular carcinoma based on molecular features. Gastroenterology 153(3):812–826. https://​doi.​org/​10.​1053/​j.​gastro.​2017.​06.​007 CrossRefPubMed
12.
Zurück zum Zitat Chen YP, Wang YQ, Lv JW, Li YQ, Chua MLK, Le QT, Lee N, Colevas AD, Seiwert T, Hayes DN, Riaz N, Vermorken JB, O'Sullivan B, He QM, Yang XJ, Tang LL, Mao YP, Sun Y, Liu N, Ma J (2019) Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy. Ann Oncol Off J Eur Soc Med Oncol 30(1):68–75. https://doi.org/10.1093/annonc/mdy470 CrossRef Chen YP, Wang YQ, Lv JW, Li YQ, Chua MLK, Le QT, Lee N, Colevas AD, Seiwert T, Hayes DN, Riaz N, Vermorken JB, O'Sullivan B, He QM, Yang XJ, Tang LL, Mao YP, Sun Y, Liu N, Ma J (2019) Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy. Ann Oncol Off J Eur Soc Med Oncol 30(1):68–75. https://​doi.​org/​10.​1093/​annonc/​mdy470 CrossRef
20.
Zurück zum Zitat Magnuson AM, Kiner E, Ergun A, Park JS, Asinovski N, Ortiz-Lopez A, Kilcoyne A, Paoluzzi-Tomada E, Weissleder R, Mathis D, Benoist C (2018) Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types. Proc Natl Acad Sci USA 115(45):E10672–e10681. https://doi.org/10.1073/pnas.1810580115 CrossRefPubMed Magnuson AM, Kiner E, Ergun A, Park JS, Asinovski N, Ortiz-Lopez A, Kilcoyne A, Paoluzzi-Tomada E, Weissleder R, Mathis D, Benoist C (2018) Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types. Proc Natl Acad Sci USA 115(45):E10672–e10681. https://​doi.​org/​10.​1073/​pnas.​1810580115 CrossRefPubMed
21.
Zurück zum Zitat Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N (2015) Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160(1–2):48–61CrossRef Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N (2015) Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160(1–2):48–61CrossRef
22.
Zurück zum Zitat McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469CrossRef McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469CrossRef
23.
Zurück zum Zitat Davoli T, Uno H, Wooten EC, Elledge SJ (2017) Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science 355(6322):eaaf8399CrossRef Davoli T, Uno H, Wooten EC, Elledge SJ (2017) Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science 355(6322):eaaf8399CrossRef
26.
Zurück zum Zitat Lin SJ, Gagnon-Bartsch JA, Tan IB, Earle S, Ruff L, Pettinger K, Ylstra B, van Grieken N, Rha SY, Chung HC, Lee JS, Cheong JH, Noh SH, Aoyama T, Miyagi Y, Tsuburaya A, Yoshikawa T, Ajani JA, Boussioutas A, Yeoh KG, Yong WP, So J, Lee J, Kang WK, Kim S, Kameda Y, Arai T, Zur Hausen A, Speed TP, Grabsch HI, Tan P (2015) Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut 64(11):1721–1731. https://doi.org/10.1136/gutjnl-2014-308252 CrossRefPubMed Lin SJ, Gagnon-Bartsch JA, Tan IB, Earle S, Ruff L, Pettinger K, Ylstra B, van Grieken N, Rha SY, Chung HC, Lee JS, Cheong JH, Noh SH, Aoyama T, Miyagi Y, Tsuburaya A, Yoshikawa T, Ajani JA, Boussioutas A, Yeoh KG, Yong WP, So J, Lee J, Kang WK, Kim S, Kameda Y, Arai T, Zur Hausen A, Speed TP, Grabsch HI, Tan P (2015) Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut 64(11):1721–1731. https://​doi.​org/​10.​1136/​gutjnl-2014-308252 CrossRefPubMed
28.
Zurück zum Zitat Panda A, Mehnert JM, Hirshfield KM, Riedlinger G, Damare S, Saunders T, Kane M, Sokol L, Stein MN, Poplin E, Rodriguez-Rodriguez L, Silk AW, Aisner J, Chan N, Malhotra J, Frankel M, Kaufman HL, Ali S, Ross JS, White EP, Bhanot G, Ganesan S (2018) Immune activation and benefit from avelumab in EBV-positive gastric cancer. J Natl Cancer Inst 110(3):316–320. https://doi.org/10.1093/jnci/djx213 CrossRefPubMed Panda A, Mehnert JM, Hirshfield KM, Riedlinger G, Damare S, Saunders T, Kane M, Sokol L, Stein MN, Poplin E, Rodriguez-Rodriguez L, Silk AW, Aisner J, Chan N, Malhotra J, Frankel M, Kaufman HL, Ali S, Ross JS, White EP, Bhanot G, Ganesan S (2018) Immune activation and benefit from avelumab in EBV-positive gastric cancer. J Natl Cancer Inst 110(3):316–320. https://​doi.​org/​10.​1093/​jnci/​djx213 CrossRefPubMed
30.
Zurück zum Zitat Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S, Park SH, Park JO, Park YS, Lim HY, Lee H, Choi M, Talasaz A, Kang PS, Cheng J, Loboda A, Lee J, Kang WK (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med 24(9):1449–1458. https://doi.org/10.1038/s41591-018-0101-z CrossRefPubMed Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S, Park SH, Park JO, Park YS, Lim HY, Lee H, Choi M, Talasaz A, Kang PS, Cheng J, Loboda A, Lee J, Kang WK (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med 24(9):1449–1458. https://​doi.​org/​10.​1038/​s41591-018-0101-z CrossRefPubMed
31.
Zurück zum Zitat Wang F, Wei XL, Wang FH, Xu N, Shen L, Dai GH, Yuan XL, Chen Y, Yang SJ, Shi JH, Hu XC, Lin XY, Zhang QY, Feng JF, Ba Y, Liu YP, Li W, Shu YQ, Jiang Y, Li Q, Wang JW, Wu H, Feng H, Yao S, Xu RH (2019) Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432. Ann Oncol. https://doi.org/10.1093/annonc/mdz197 CrossRefPubMedPubMedCentral Wang F, Wei XL, Wang FH, Xu N, Shen L, Dai GH, Yuan XL, Chen Y, Yang SJ, Shi JH, Hu XC, Lin XY, Zhang QY, Feng JF, Ba Y, Liu YP, Li W, Shu YQ, Jiang Y, Li Q, Wang JW, Wu H, Feng H, Yao S, Xu RH (2019) Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432. Ann Oncol. https://​doi.​org/​10.​1093/​annonc/​mdz197 CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Liu L, Bai X, Wang J, Tang XR, Wu DH, Du SS, Du XJ, Zhang YW, Zhu HB, Fang Y, Guo ZQ, Zeng Q, Guo XJ, Liu Z, Dong ZY (2019) Combination of TMB and CNA stratifies prognostic and predictive responses to immunotherapy across metastatic cancer. Clin Cancer Res Off J Am Assoc Cancer Res 25(24):7413–7423. https://doi.org/10.1158/1078-0432.CCR-19-0558 CrossRef Liu L, Bai X, Wang J, Tang XR, Wu DH, Du SS, Du XJ, Zhang YW, Zhu HB, Fang Y, Guo ZQ, Zeng Q, Guo XJ, Liu Z, Dong ZY (2019) Combination of TMB and CNA stratifies prognostic and predictive responses to immunotherapy across metastatic cancer. Clin Cancer Res Off J Am Assoc Cancer Res 25(24):7413–7423. https://​doi.​org/​10.​1158/​1078-0432.​CCR-19-0558 CrossRef
38.
Zurück zum Zitat Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q (2019) Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res Off J Am Assoc Cancer Res 25(2):515–523. https://doi.org/10.1158/1078-0432.CCR-18-2484 CrossRef Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q (2019) Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res Off J Am Assoc Cancer Res 25(2):515–523. https://​doi.​org/​10.​1158/​1078-0432.​CCR-18-2484 CrossRef
39.
Zurück zum Zitat Chen YP, Wang YQ, Lv JW, Li YQ, Chua MLK, Le QT, Lee N, Colevas AD, Seiwert T, Hayes DN, Riaz N, Vermorken JB, O'Sullivan B, He QM, Yang XJ, Tang LL, Mao YP, Sun Y, Liu N, Ma J (2018) Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy. Ann Oncol. https://doi.org/10.1093/annonc/mdy470 CrossRefPubMedPubMedCentral Chen YP, Wang YQ, Lv JW, Li YQ, Chua MLK, Le QT, Lee N, Colevas AD, Seiwert T, Hayes DN, Riaz N, Vermorken JB, O'Sullivan B, He QM, Yang XJ, Tang LL, Mao YP, Sun Y, Liu N, Ma J (2018) Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy. Ann Oncol. https://​doi.​org/​10.​1093/​annonc/​mdy470 CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469. https://doi.org/10.1126/science.aaf1490 CrossRefPubMedPubMedCentral McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469. https://​doi.​org/​10.​1126/​science.​aaf1490 CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan AS, Tsui WY, Lee SP, Ho SL, Chan AK, Cheng GH, Roberts PC, Rejto PA, Gibson NW, Pocalyko DJ, Mao M, Xu J, Leung SY (2011) Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 43(12):1219–1223. https://doi.org/10.1038/ng.982 CrossRefPubMed Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan AS, Tsui WY, Lee SP, Ho SL, Chan AK, Cheng GH, Roberts PC, Rejto PA, Gibson NW, Pocalyko DJ, Mao M, Xu J, Leung SY (2011) Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 43(12):1219–1223. https://​doi.​org/​10.​1038/​ng.​982 CrossRefPubMed
43.
Zurück zum Zitat Soundararajan C, Fradette JJ, Konen JM, Moulder S, Zhang X, Gibbons DL, Varadarajan N, Wistuba II, Tripathy D, Bernatchez C, Byers LA, Chang JT, Contreras A, Lim B, Parra ER, Roarty EB, Wang J, Yang F, Barton M, Rosen JM, Mani SA (2019) Targeting the interplay between epithelial-to-mesenchymal-transition and the immune system for effective immunotherapy. Cancers (Basel). https://doi.org/10.3390/cancers11050714 CrossRef Soundararajan C, Fradette JJ, Konen JM, Moulder S, Zhang X, Gibbons DL, Varadarajan N, Wistuba II, Tripathy D, Bernatchez C, Byers LA, Chang JT, Contreras A, Lim B, Parra ER, Roarty EB, Wang J, Yang F, Barton M, Rosen JM, Mani SA (2019) Targeting the interplay between epithelial-to-mesenchymal-transition and the immune system for effective immunotherapy. Cancers (Basel). https://​doi.​org/​10.​3390/​cancers11050714 CrossRef
44.
Zurück zum Zitat Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, Makarev E, Artemov AV, Wysocki PT, Mehra R, Nimmagadda S, Marchionni L, Sidransky D, Borrello IM, Izumchenko E, Bedi A (2018) Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat Commun 9(1):741. https://doi.org/10.1038/s41467-017-02696-6 CrossRefPubMedPubMedCentral Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, Makarev E, Artemov AV, Wysocki PT, Mehra R, Nimmagadda S, Marchionni L, Sidransky D, Borrello IM, Izumchenko E, Bedi A (2018) Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat Commun 9(1):741. https://​doi.​org/​10.​1038/​s41467-017-02696-6 CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL (2018) Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ advanced solid tumors. Clin Cancer Res 24(6):1287–1295. https://doi.org/10.1158/1078-0432.CCR-17-2653 CrossRefPubMed Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL (2018) Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ advanced solid tumors. Clin Cancer Res 24(6):1287–1295. https://​doi.​org/​10.​1158/​1078-0432.​CCR-17-2653 CrossRefPubMed
Metadaten
Titel
Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications
verfasst von
Yu-Jie Zhou
Gui-Qi Zhu
Xiao-Fan Lu
Kenneth I. Zheng
Qi-Wen Wang
Jin-Nan Chen
Qing-Wei Zhang
Fang-Rong Yan
Xiao-Bo Li
Publikationsdatum
25.02.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02525-8

Weitere Artikel der Ausgabe 6/2020

Cancer Immunology, Immunotherapy 6/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.