REFERENCES
1. 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.
2. Wagner AD, Syn NL, Moehler M, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017;8:CD004064.
3. Xie J, Fu L, Jin L. Immunotherapy of gastric cancer: past, future perspective and challenges. Pathol Res Pract. 2021;218:153322.
4. Yu X, Zhai X, Wu J, et al. Evolving perspectives regarding the role of the PD-1/PD-L1 pathway in gastric cancer immunotherapy. Biochim Biophys Acta Mol Basis Dis. 2024;1870:166881.
5. Fuchs CS, Doi T, Jang RW, 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.
6. Lei M, Siemers NO, Pandya D, et al. Analyses of PD-L1 and inflammatory gene expression association with efficacy of nivolumab ± ipilimumab in gastric cancer/gastroesophageal junction cancer. Clin Cancer Res. 2021;27:3926-35.
7. Xu J, Jiang H, Pan Y, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial. JAMA. 2023;330:2064-74.
8. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40.
9. Wainberg ZA, Fuchs CS, Tabernero T, et al. Efficacy of pembrolizumab (pembro) monotherapy versus chemotherapy for PD-L1-positive (CPS ≥10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies. J Clin Oncol. 2020;38:4.
10. Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17:717-26.
11. Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol. 2018;36:2836-44.
12. Chen LT, Satoh T, Ryu MH, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020;23:510-9.
13. Bang YJ, Ruiz EY, Van Cutsem E, et al. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018;29:2052-60.
14. Shitara K, Özgüroğlu M, Bang YJ, 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;392:123-33.
15. Xu J, Jiang H, Pan Y, et al. LBA53 Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): First results of a randomized, double-blind, phase III study. Ann Oncol. 2021;32:S1331.
16. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915-28.
17. Kang YK, Chen LT, Ryu MH, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:234-47.
18. Yamaguchi K, Minashi K, Sakai D, et al. Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer. Cancer Sci. 2022;113:2814-27.
19. Rha SY, Oh DY, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24:1181-95.
20. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023;402:2197-208.
21. Li S, Yu W, Xie F, et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nat Commun. 2023;14:8.
22. Tang Z, Wang Y, Liu D, et al. The neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nat Commun. 2022;13:6807.
23. Kelly RJ, Landon BV, Zaidi AH, et al. Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses. Nat Med. 2024;30:1023-34.
24. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol. 2021;39:2339-49.
25. Boll LM, Vázquez Montes de Oca S, Camarena ME, et al. Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts. Nat Commun. 2025;16:1213.
26. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67-76.
27. Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018;391:748-57.
28. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21:1353-65.
29. Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021;71:264-79.
30. Wu Y, Xu J, Du C, et al. The predictive value of tumor mutation burden on efficacy of immune checkpoint inhibitors in cancers: a systematic review and meta-analysis. Front Oncol. 2019;9:1161.
31. Xiang K, Zhang M, Yang B, et al. TM-score predicts immunotherapy efficacy and improves the performance of the machine learning prognostic model in gastric cancer. Int Immunopharmacol. 2024;134:112224.
32. Wang F, Wei XL, Wang FH, et al. Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432. Ann Oncol. 2019;30:1479-86.
33. Mishima S, Kawazoe A, Nakamura Y, et al. Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer. J Immunother Cancer. 2019;7:24.
35. Zeng D, Li M, Zhou R, et al. Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures. Cancer Immunol Res. 2019;7:737-50.
36. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018;24:1449-58.
37. Sun YT, Guan WL, Zhao Q, et al. PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial. Am J Cancer Res. 2021;11:5006-15.
38. Qiu MZ, Wang C, Wu Z, et al. Dynamic single-cell mapping unveils Epstein-Barr virus-imprinted T-cell exhaustion and on-treatment response. Signal Transduct Target Ther. 2023;8:370.
39. El Helali A, Tao J, Wong CHL, et al. A meta-analysis with systematic review: efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer. Front Oncol. 2022;12:908026.
40. Pietrantonio F, Randon G, Di Bartolomeo M, et al. Predictive role of microsatellite instability for PD-1 blockade in patients with advanced gastric cancer: a meta-analysis of randomized clinical trials. ESMO Open. 2021;6:100036.
41. Ooki A, Osumi H, Yoshino K, Yamaguchi K. Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair. Gastric Cancer. 2024;27:907-31.
42. André T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: the GERCOR NEONIPIGA phase II study. J Clin Oncol. 2023;41:255-65.
43. Pietrantonio F, Raimondi A, Lonardi S, et al. INFINITY: a multicentre, single-arm, multi-cohort, phase II trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). JCO. 2023;41:358-358.
44. Nikanjam M, Kato S, Kurzrock R. Liquid biopsy: current technology and clinical applications. J Hematol Oncol. 2022;15:131.
45. Ma S, Zhou M, Xu Y, et al. Clinical application and detection techniques of liquid biopsy in gastric cancer. Mol Cancer. 2023;22:7.
46. Maron SB, Chase LM, Lomnicki S, et al. Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma. Clin Cancer Res. 2019;25:7098-112.
47. Jin Y, Chen DL, Wang F, et al. The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors. Mol Cancer. 2020;19:154.
48. Meng Q, Lu YX, Ruan DY, et al. DNA methylation regulator-mediated modification patterns and tumor microenvironment characterization in gastric cancer. Mol Ther Nucleic Acids. 2021;24:695-710.
49. Zhang M, Qi C, Wang Z, et al. Molecular characterization of ctDNA from Chinese patients with advanced gastric adenocarcinoma reveals actionable alterations for targeted and immune therapy. J Mol Med. 2021;99:1311-21.
50. Kawazoe A, Shitara K, Boku N, Yoshikawa T, Terashima M. Current status of immunotherapy for advanced gastric cancer. Jpn J Clin Oncol. 2021;51:20-7.
51. Xu Z, Zeng S, Gong Z, Yan Y. Exosome-based immunotherapy: a promising approach for cancer treatment. Mol Cancer. 2020;19:160.
52. Li Z, Suo B, Long G, et al. Exosomal miRNA-16-5p derived from M1 macrophages enhances T cell-dependent immune response by regulating PD-L1 in gastric cancer. Front Cell Dev Biol. 2020;8:572689.
53. Jiang Y, Wang Y, Chen G, et al. Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer. Cell Metab. 2024;36:1806-22.e11.
54. Tian T, Liang R, Erel-Akbaba G, et al. Immune checkpoint inhibition in GBM primed with radiation by engineered extracellular vesicles. ACS Nano. 2022;16:1940-53.
55. Zuo B, Qi H, Lu Z, et al. Alarmin-painted exosomes elicit persistent antitumor immunity in large established tumors in mice. Nat Commun. 2020;11:1790.
56. Li TT, Liu H, Yu J, Shi GY, Zhao LY, Li GX. Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells. World J Gastroenterol. 2018;24:2236-46.
57. Garajová I, Balsano R, Wang H, et al. The role of the microbiome in drug resistance in gastrointestinal cancers. Expert Rev Anticancer Ther. 2021;21:165-76.
58. Che H, Xiong Q, Ma J, et al. Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors. BMC Cancer. 2022;22:904.
59. Han Z, Cheng S, Dai D, et al. The gut microbiome affects response of treatments in HER2-negative advanced gastric cancer. Clin Transl Med. 2023;13:e1312.
60. Griffin ME, Espinosa J, Becker JL, et al. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy. Science. 2021;373:1040-6.
61. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084-9.
62. Lee SY, Jhun J, Woo JS, et al. Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer. Gut Microbes. 2024;16:2300846.
63. Coutzac C, Jouniaux JM, Paci A, et al. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun. 2020;11:2168.
64. Yang Y, Dai D, Jin W, et al. Microbiota and metabolites alterations in proximal and distal gastric cancer patients. J Transl Med. 2022;20:439.
65. Cheng S, Han Z, Dai D, et al. Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy. Cell Rep Med. 2024;5:101355.
66. Karkhah A, Ebrahimpour S, Rostamtabar M, et al. Helicobacter pylori evasion strategies of the host innate and adaptive immune responses to survive and develop gastrointestinal diseases. Microbiol Res. 2019;218:49-57.
67. Magahis PT, Maron SB, Cowzer D, et al. Impact of Helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J Immunother Cancer. 2023;11:e007699.
68. Jia K, Chen Y, Xie Y, et al. Helicobacter pylori and immunotherapy for gastrointestinal cancer. Innovation. 2024;5:100561.
69. Holokai L, Chakrabarti J, Broda T, et al. Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection. PLoS Pathog. 2019;15:e1007468.
70. Heimesaat MM, Fischer A, Plickert R, et al. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils. PLoS One. 2014;9:e100362.
71. Liu L, Shah K. The potential of the gut microbiome to reshape the cancer therapy paradigm: a review. JAMA Oncol. 2022;8:1059-67.
72. Huang W, Jiang Y, Xiong W, et al. Noninvasive imaging of the tumor immune microenvironment correlates with response to immunotherapy in gastric cancer. Nat Commun. 2022;13:5095.
73. He H, Qi X, Fu H, et al. Imaging diagnosis and efficacy monitoring by [89Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies. Theranostics. 2024;14:392-405.
74. Rong X, Lv J, Liu Y, et al. PET/CT imaging of activated cancer-associated fibroblasts predict response to PD-1 blockade in gastric cancer patients. Front Oncol. 2021;11:802257.
75. Jiang Y, Zhou K, Sun Z, et al. Non-invasive tumor microenvironment evaluation and treatment response prediction in gastric cancer using deep learning radiomics. Cell Rep Med. 2023;4:101146.
76. Huynh E, Hosny A, Guthier C, et al. Artificial intelligence in radiation oncology. Nat Rev Clin Oncol. 2020;17:771-81.
77. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36:1714-68.
78. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158-68.
79. Masuda K, Shoji H, Nagashima K, et al. Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab. BMC Cancer. 2019;19:974.
80. Zhang X, Xu S, Wang J, et al. Are anti-PD-1-associated immune related adverse events a harbinger of favorable clinical prognosis in patients with gastric cancer? BMC Cancer. 2022;22:1136.
81. Zhou X, Yao Z, Yang H, Liang N, Zhang X, Zhang F. Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis. BMC Med. 2020;18:87.
82. Hu G, Tu W, Yang L, Peng G, Yang L. ARID1A deficiency and immune checkpoint blockade therapy: from mechanisms to clinical application. Cancer Lett. 2020;473:148-55.
83. Chen Q, Du X, Hu S, Huang Q. NF-κB-related metabolic gene signature predicts the prognosis and immunotherapy response in gastric cancer. Biomed Res Int. 2022;2022:5092505.
84. Tong M, Wang J, He W, et al. Predictive biomarkers for tumor immune checkpoint blockade. Cancer Manag Res. 2018;10:4501-7.
85. Zeng D, Wu J, Luo H, et al. Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer. J Immunother Cancer. 2021;9:e002467.
86. Mori T, Tanaka H, Suzuki S, et al. Tertiary lymphoid structures show infiltration of effective tumor-resident T cells in gastric cancer. Cancer Sci. 2021;112:1746-57.
87. Jiang Q, Tian C, Wu H, et al. Tertiary lymphoid structure patterns predicted anti-PD1 therapeutic responses in gastric cancer. Chin J Cancer Res. 2022;34:365-82.
88. Chen Y, Jia K, Sun Y, et al. Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nat Commun. 2022;13:4851.
89. Hu X, Wang Z, Wang Q, et al. Molecular classification reveals the diverse genetic and prognostic features of gastric cancer: A multi-omics consensus ensemble clustering. Biomed Pharmacother. 2021;144:112222.
90. Shi J, Wu Z, Wu X, et al. Characterization of glycometabolism and tumor immune microenvironment for predicting clinical outcomes in gastric cancer. iScience. 2023;26:106214.
91. Yoo SK, Chowell D, Valero C, Morris LGT, Chan TA. Outcomes among patients with or without obesity and with cancer following treatment with immune checkpoint blockade. JAMA Netw Open. 2022;5:e220448.
92. Namikawa T, Yokota K, Tanioka N, et al. Systemic inflammatory response and nutritional biomarkers as predictors of nivolumab efficacy for gastric cancer. Surg Today. 2020;50:1486-95.
93. Chen Y, Zhang C, Peng Z, et al. Association of lymphocyte-to-monocyte ratio with survival in advanced gastric cancer patients treated with immune checkpoint inhibitor. Front Oncol. 2021;11:589022.
