Research progress on ICIs therapy for gastric cancer and biomarkers for predicting therapeutic efficacy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHOU Baiquan ^1,2 , TANG Yufan ^1,2 , LIU Lin ^1,2 , WEN Bingbing ^1,3 , LIU Jixiang ^1,3 , LI Luyao ^1,4 ,  FAN Ruifang ¹

1. Department of General Surgery, The 940th Hospital of the Joint Support Force of the People’s Liberation Army of China, Lanzhou 730030, P. R. China;
2. The First Clinical College of Gansu University of Chinese Medicine, Lanzhou 730030, P. R. China;
3. Medical Department of Northwest Minzu University, Lanzhou 730030, P. R. China;
4. The Second Clinical College of Lanzhou University, Lanzhou 730030, P. R. China;

Corresponding author：

FAN Ruifang, Email: fanruif@163.com

Keywords：

gastric cancer; immune checkpoint inhibitors; immunotherapy; biomarkers

DOI：

10.7507/1007-9424.202503004

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the latest research progress in immune checkpoint inhibitors (ICIs) treatment and efficacy prediction biomarkers for gastric cancer. Methods Relevant studies on ICIs treatment and efficacy prediction biomarkers for gastric cancer in recent years at home and abroad were collected and summarized. Results ICIs combined with chemotherapy, ICIs combined with targeted therapy, chemotherapy combined with ICIs and anti-angiogenic drugs, ICIs dual immunotherapy, etc. in the first-line treatment of gastric cancer, as well as ICIs monotherapy, ICIs combined with anti-angiogenic drugs or addition of chemotherapy in the second-line treatment, have become important first- and second-line treatment methods for gastric cancer in clinical practice. Emerging immune checkpoints such as lymphocyte activation gene-3 and V-domain immunoglobulin suppressor of T-cell activation factor also have good clinical prospects; In recent years, researches on new biomarkers such as Epstein-Barr virus, helicobater pylori, tumor-infiltrating lymphocytes, liquid biopsy biomarkers have also made some progresses. Conclusions In the future, through multi-dimensional or dynamic biomarker detection, gastric cancer immunotherapy can move towards precision and individualization, maximizing the survival benefits of gastric cancer patients.

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	李茁钰, 刘凯, 张维汉, 等. 全球及中国胃癌的流行病学特点及趋势: 2018-2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(10): 1236-1245.
3.	Zeng H, Ran X, An L, et al. Disparities in stage at diagnosis for five common cancers in China: a multicentre, hospital-based, observational study. Lancet Public Health, 2021, 6(12): e877-e887. doi: 10.1016/S2468-2667(21)00157-2.
4.	Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol, 2022, 33(10): 1005-1020.
5.	Ajani JA, D'Amico TA, Bentrem DJ, et al. Gastric cancer, version 2. 2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2022, 20(2): 167-192.
6.	Wang FH, Zhang XT, Tang L, et al. The chinese society of clinical oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond), 2024, 44(1): 127-172.
7.	Janjigian YY, Ajani JA, Moehler M, et al. First-line Nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III checkmate 649 trial. J Clin Oncol, 2024, 42(17): 2012-2020.
8.	Boku N, Omori T, Shitara K, et al. Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial. Gastric Cancer, 2024, 27(6): 1287-1301.
9.	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(21): 2064-2074.
10.	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(11): 1181-1195.
11.	Qiu MZ, Oh DY, Kato K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ, 2024, 385: e078876. doi: 10.1136/bmj-2023-078876.
12.	Zhang X, Wang J, Wang G, et al. First-line sugemalimab plus chemotherapy for advanced gastric cancer: the GEMSTONE-303 randomized clinical trial. JAMA, 2025, 333(15): 1305-1314.
13.	Qin S, Bai Y, Li J, et al. First-line pembrolizumab plus chemotherapy for HER2-negative advanced gastric cancer: China subgroup analysis of the randomized phase 3 KEYNOTE-859 study. Adv Ther, 2025, 42(4): 1892-1906.
14.	Li W, Wan L. Cost-utility of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction cancer in China. Expert Rev Pharmacoecon Outcomes Res, 2024, 24(5): 671-678.
15.	Xu L, Long Y, Yao L, et al. Updated cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma. Front Oncol, 2024, 14: 1477722. doi: 10.3389/fonc.2024.1477722.
16.	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(10418): 2197-2208.
17.	Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab in HER2-positive gastric cancer. N Engl J Med, 2024, 391(14): 1360-1362.
18.	Deng T, Wang F, Zhang L, et al. Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study. Cancer Immunol Immunother, 2024, 73(8): 154. doi: 10.1007/s00262-024-03743-0.
19.	Wang Y, Lu J, Chong X, et al. PD-1 antibody camrelizumab plus apatinib and SOX as first-line treatment in patients with AFP-producing gastric or gastro-esophageal junction adenocarcinoma (CAP 06): a multi-center, single-arm, phase 2 trial. Signal Transduct Target Ther, 2025, 10(1): 100. doi: 10.1038/s41392-025-02193-z.
20.	Shitara K, Ajani JA, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature, 2022, 603(7903): 942-948.
21.	Muro K, Kawakami H, Kadowaki S, et al. 1513MO A phase Ⅱ study of nivolumab plus low dose ipilimumab as first-line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: first results of the NO LIMIT study (WJOG13320G/CA209-7W7). Ann Oncol, 2023, 34: s852-s853. doi: 10.1016/j.annonc.2023.09.1426.
22.	Shen L, Li J, Deng Y, et al. Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency. 2020 ASCO, abatract 3021.
23.	Li J, Qin S, Zhong H, et al. Updated efficacy and safety results from the phase 2 study of serplulimab, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors. 2022 ASCO, abstract 2592.
24.	Li J, Xu Y, Zang A, et al. Long-term follow-up of a phase II study of tislelizumab (TIS) monotherapy in patients (pts) with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors. Annals of Oncology, 2023, 34(S2): S640. doi: 10.1016/j.annonc.2023.09.2196.
25.	Wei Q, Xu X, Li J, et al. Apatinib plus toripalimab (anti-PD1 therapy) as second-line therapy in patients with advanced gastric or esophagogastric junction cancer: results from a randomized, open-label phase II study. Oncologist, 2024, 29(4): 364-e578. doi: 10.1093/oncolo/oyae005.
26.	Zhang L, Wang W, Ge S, et al. Sintilimab plus apatinib and chemotherapy as second-/third-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: a prospective, single-arm, phase II trial. BMC Cancer, 2023, 23(1): 211. doi: 10.1186/s12885-023-10661-4.
27.	Tougeron D, Dahan L, Evesque L, et al. FOLFIRI plus durvalumab with or without tremelimumab in second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: the PRODIGE 59-FFCD 1707-DURIGAST randomized clinical trial. JAMA Oncol, 2024, 10(6): 709-717.
28.	Wei J, Zhang P, Hu Q, et al. Nab-paclitaxel combined with cadonilimab (AK104) as second-line treatment for advanced gastric cancer: protocol for a phase II prospective, multicenter, single-arm clinical trial. Front Immunol, 2025, 16: 1519545. doi: 10.3389/fimmu.2025.1519545.
29.	Mao C, Xiong A, Qian J, et al. Dual inhibition of LAG-3 and PD-1 with IBI110 and sintilimab in advanced solid tumors: the first-in-human phase Ia/Ib study. J Hematol Oncol, 2024, 17(1): 132. doi: 10.1186/s13045-024-01651-5.
30.	Ku G, Haag GM, Park H, et al. Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study. ESMO Open, 2025, 10(2): 104107. doi: 10.1016/j.esmoop.2024.104107.
31.	Hegewisch-Becker S, Mendez G, Chao J, et al. First-line nivolumab and relatlimab plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma: the phase II RELATIVITY-060 study. J Clin Oncol, 2024, 42(17): 2080-2093.
32.	Seghers S, Domen A, Prenen H. Challenges and prospects of LAG-3 inhibition in advanced gastric and gastroesophageal junction cancer: insights from the RELATIVITY-060 trial. J Gastrointest Oncol, 2024, 15(6): 2735-2738.
33.	Cao Y, Yu K, Zhang Z, et al. Blockade of V-domain immunoglobulin suppressor of T-cell activation reprograms tumour-associated macrophages and improves efficacy of PD-1 inhibitor in gastric cancer. Clin Transl Med, 2024, 14(2): e1578. doi: 10.1002/ctm2.1578.
34.	Nishizaki D, Kurzrock R, Miyashita H, et al. Viewing the immune checkpoint VISTA: landscape and outcomes across cancers. ESMO Open, 2024, 9(4): 102942. doi: 10.1016/j.esmoop.2024.102942.
35.	Noori M, Fayyaz F, Zali MR, et al. Predictive value of PD-L1 expression in response to immune checkpoint inhibitors for gastric cancer treatment: a systematic review and meta-analysis. Expert Rev Anticancer Ther, 2023, 23(9): 1029-1039.
36.	Yoon HH, Jin Z, Kour O, et al. Association of PD-L1 expression and other variables with benefit from immune checkpoint inhibition in advanced gastroesophageal cancer: systematic review and meta-analysis of 17 phase 3 randomized clinical trials. JAMA Oncol, 2022, 8(10): 1456-1465.
37.	Li JB, Lai MY, Lin ZC, et al. The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis. Cancer Immunol Immunother, 2024, 73(7): 132. doi: 10.1007/s00262-024-03726-1.
38.	Huang C, Ren S, Chen Y, et al. PD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance. Sci Adv, 2023, 9(21): eade4186. 10.1126/sciadv. ade4186.
39.	Komori A, Hironaka S, Kadowaki S, et al. Prevalence and clinicopathological features of microsatellite instability-high metastatic or recurrent gastric and esophagogastric junction cancer: WJOG13320GPS. Gastric Cancer, 2025, 28(2): 301-308.
40.	Ooki A, Osumi H, Yoshino K, et al. Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair. Gastric Cancer, 2024, 27(5): 907-931.
41.	Landre T, Des Guetz G. Microsatellite instability-high status as a pan-cancer biomarker for immunotherapy efficacy. Cancer Immunol Immunother, 2025, 74(4): 122. doi: 10.1007/s00262-025-03980-x.
42.	Ke L, Li S, Huang D. The predictive value of tumor mutation burden on survival of gastric cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Int Immunopharmacol, 2023, 124(Pt B): 110986. doi: 10.1016/j.intimp.2023.110986.
43.	Lee KW, Van Cutsem E, Bang YJ, et al. Association of tumor mutational burden with efficacy of pembrolizumab±chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res, 2022, 28(16): 3489-3498.
44.	Wang J, Xiu J, Farrell A, et al. Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study. Lancet Oncol, 2023, 24(2): 151-161.
45.	Yee EJ, Gilbert D, Kaplan J, et al. Immune landscape of Epstein-Barr Virus-associated gastric cancer: analysis from a western academic institution. J Surg Res, 2024, 296: 742-750.
46.	Kondo A, Shinozaki-Ushiku A, Rokutan H, et al. Loss of viral genome with altered immune microenvironment during tumour progression of Epstein-Barr virus-associated gastric carcinoma. J Pathol, 2023, 260(2): 124-136.
47.	Li LL, Yu AY, Zhu M, et al. Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer. Arch Virol, 2024, 169(5): 114. doi: 10.1007/s00705-024-06033-3.
48.	Xie T, Liu Y, Zhang Z, et al. Positive status of Epstein-Barr Virus as a biomarker for gastric cancer immunotherapy: a prospective observational study. J Immunother, 2020, 43(4): 139-144.
49.	Bai Y, Xie T, Wang Z, et al. Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer. J Immunother Cancer, 2022, 10(3): e004080. doi: 10.1136/jitc-2021-004080.
50.	Ziogou A, Giannakodimos A, Giannakodimos I, et al. Effect of helicobacter pylori infection on immunotherapy for gastrointestinal cancer: a narrative review. Immunotherapy, 2025, 17(5): 355-368.
51.	Jia K, Chen Y, Xie Y, et al. Helicobacter pylori and immunotherapy for gastrointestinal cancer. Innovation (Camb), 2024, 5(2): 100561. doi: 10.1016/j.xinn.2023.100561.
52.	Gong X, Shen L, Xie J, et al. Helicobacter pylori infection reduces the efficacy of cancer immunotherapy: A systematic review and meta-analysis. Helicobacter, 2023, 28(6): e13011. doi: 10.1111/hel.13011.
53.	Yu B, Peppelenbosch M, Fuhler G. Impact of helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J Immunother Cancer, 2024, 12(1): e008422. doi: 10.1136/jitc-2023-008422.
54.	Yu B, Peppelenbosch M, Fuhler G. Impact of helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J Immunother Cancer, 2024, 12(1): e008422. doi: 10.1136/jitc-2023-008422.
55.	Verschoor YL, van de Haar J, van den Berg JG, et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med, 2024, 30(2): 519-530.
56.	Yin J, Yuan J, Li Y, et al. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med, 2023, 29(8): 2068-2078.
57.	Chen X, Xu H, Chen X, et al. First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study. Signal Transduct Target Ther, 2024, 9(1): 73. doi: 10.1038/s41392-024-01773-9.
58.	Fagery M, Khorshidi HA, Wong SQ, et al. Health economic evidence and modeling challenges for liquid biopsy assays in cancer management: a systematic literature review. Pharmacoeconomics, 2023, 41(10): 1229-1248.
59.	Zhang Z, Wu H, Chong W, et al. Liquid biopsy in gastric cancer: predictive and prognostic biomarkers. Cell Death Dis, 2022, 13(10): 903. doi: 10.1038/s41419-022-05350-2.
60.	Zhang H, Jin T, Peng Y, et al. Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis. Int J Surg, 2024, 110(7): 4370-4381.
61.	Min L, Chen J, Yu M, et al. Utilizing circulating tumour DNA as a prognostic predictor of gastric cancer: a meta-analysis. Biomarkers, 2023, 28(5): 427-436.
62.	Cui Q, Li W, Wang D, et al. Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis. World J Surg Oncol, 2023, 21(1): 318. doi: 10.1186/s12957-023-03215-2.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. 李茁钰, 刘凯, 张维汉, 等. 全球及中国胃癌的流行病学特点及趋势: 2018-2022《全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(10): 1236-1245.
3. Zeng H, Ran X, An L, et al. Disparities in stage at diagnosis for five common cancers in China: a multicentre, hospital-based, observational study. Lancet Public Health, 2021, 6(12): e877-e887. doi: 10.1016/S2468-2667(21)00157-2.
4. Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol, 2022, 33(10): 1005-1020.
5. Ajani JA, D'Amico TA, Bentrem DJ, et al. Gastric cancer, version 2. 2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2022, 20(2): 167-192.
6. Wang FH, Zhang XT, Tang L, et al. The chinese society of clinical oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond), 2024, 44(1): 127-172.
7. Janjigian YY, Ajani JA, Moehler M, et al. First-line Nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III checkmate 649 trial. J Clin Oncol, 2024, 42(17): 2012-2020.
8. Boku N, Omori T, Shitara K, et al. Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial. Gastric Cancer, 2024, 27(6): 1287-1301.
9. 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(21): 2064-2074.
10. 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(11): 1181-1195.
11. Qiu MZ, Oh DY, Kato K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ, 2024, 385: e078876. doi: 10.1136/bmj-2023-078876.
12. Zhang X, Wang J, Wang G, et al. First-line sugemalimab plus chemotherapy for advanced gastric cancer: the GEMSTONE-303 randomized clinical trial. JAMA, 2025, 333(15): 1305-1314.
13. Qin S, Bai Y, Li J, et al. First-line pembrolizumab plus chemotherapy for HER2-negative advanced gastric cancer: China subgroup analysis of the randomized phase 3 KEYNOTE-859 study. Adv Ther, 2025, 42(4): 1892-1906.
14. Li W, Wan L. Cost-utility of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction cancer in China. Expert Rev Pharmacoecon Outcomes Res, 2024, 24(5): 671-678.
15. Xu L, Long Y, Yao L, et al. Updated cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma. Front Oncol, 2024, 14: 1477722. doi: 10.3389/fonc.2024.1477722.
16. 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(10418): 2197-2208.
17. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab in HER2-positive gastric cancer. N Engl J Med, 2024, 391(14): 1360-1362.
18. Deng T, Wang F, Zhang L, et al. Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study. Cancer Immunol Immunother, 2024, 73(8): 154. doi: 10.1007/s00262-024-03743-0.
19. Wang Y, Lu J, Chong X, et al. PD-1 antibody camrelizumab plus apatinib and SOX as first-line treatment in patients with AFP-producing gastric or gastro-esophageal junction adenocarcinoma (CAP 06): a multi-center, single-arm, phase 2 trial. Signal Transduct Target Ther, 2025, 10(1): 100. doi: 10.1038/s41392-025-02193-z.
20. Shitara K, Ajani JA, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature, 2022, 603(7903): 942-948.
21. Muro K, Kawakami H, Kadowaki S, et al. 1513MO A phase Ⅱ study of nivolumab plus low dose ipilimumab as first-line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: first results of the NO LIMIT study (WJOG13320G/CA209-7W7). Ann Oncol, 2023, 34: s852-s853. doi: 10.1016/j.annonc.2023.09.1426.
22. Shen L, Li J, Deng Y, et al. Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency. 2020 ASCO, abatract 3021.
23. Li J, Qin S, Zhong H, et al. Updated efficacy and safety results from the phase 2 study of serplulimab, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors. 2022 ASCO, abstract 2592.
24. Li J, Xu Y, Zang A, et al. Long-term follow-up of a phase II study of tislelizumab (TIS) monotherapy in patients (pts) with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors. Annals of Oncology, 2023, 34(S2): S640. doi: 10.1016/j.annonc.2023.09.2196.
25. Wei Q, Xu X, Li J, et al. Apatinib plus toripalimab (anti-PD1 therapy) as second-line therapy in patients with advanced gastric or esophagogastric junction cancer: results from a randomized, open-label phase II study. Oncologist, 2024, 29(4): 364-e578. doi: 10.1093/oncolo/oyae005.
26. Zhang L, Wang W, Ge S, et al. Sintilimab plus apatinib and chemotherapy as second-/third-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: a prospective, single-arm, phase II trial. BMC Cancer, 2023, 23(1): 211. doi: 10.1186/s12885-023-10661-4.
27. Tougeron D, Dahan L, Evesque L, et al. FOLFIRI plus durvalumab with or without tremelimumab in second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: the PRODIGE 59-FFCD 1707-DURIGAST randomized clinical trial. JAMA Oncol, 2024, 10(6): 709-717.
28. Wei J, Zhang P, Hu Q, et al. Nab-paclitaxel combined with cadonilimab (AK104) as second-line treatment for advanced gastric cancer: protocol for a phase II prospective, multicenter, single-arm clinical trial. Front Immunol, 2025, 16: 1519545. doi: 10.3389/fimmu.2025.1519545.
29. Mao C, Xiong A, Qian J, et al. Dual inhibition of LAG-3 and PD-1 with IBI110 and sintilimab in advanced solid tumors: the first-in-human phase Ia/Ib study. J Hematol Oncol, 2024, 17(1): 132. doi: 10.1186/s13045-024-01651-5.
30. Ku G, Haag GM, Park H, et al. Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study. ESMO Open, 2025, 10(2): 104107. doi: 10.1016/j.esmoop.2024.104107.
31. Hegewisch-Becker S, Mendez G, Chao J, et al. First-line nivolumab and relatlimab plus chemotherapy for gastric or gastroesophageal junction adenocarcinoma: the phase II RELATIVITY-060 study. J Clin Oncol, 2024, 42(17): 2080-2093.
32. Seghers S, Domen A, Prenen H. Challenges and prospects of LAG-3 inhibition in advanced gastric and gastroesophageal junction cancer: insights from the RELATIVITY-060 trial. J Gastrointest Oncol, 2024, 15(6): 2735-2738.
33. Cao Y, Yu K, Zhang Z, et al. Blockade of V-domain immunoglobulin suppressor of T-cell activation reprograms tumour-associated macrophages and improves efficacy of PD-1 inhibitor in gastric cancer. Clin Transl Med, 2024, 14(2): e1578. doi: 10.1002/ctm2.1578.
34. Nishizaki D, Kurzrock R, Miyashita H, et al. Viewing the immune checkpoint VISTA: landscape and outcomes across cancers. ESMO Open, 2024, 9(4): 102942. doi: 10.1016/j.esmoop.2024.102942.
35. Noori M, Fayyaz F, Zali MR, et al. Predictive value of PD-L1 expression in response to immune checkpoint inhibitors for gastric cancer treatment: a systematic review and meta-analysis. Expert Rev Anticancer Ther, 2023, 23(9): 1029-1039.
36. Yoon HH, Jin Z, Kour O, et al. Association of PD-L1 expression and other variables with benefit from immune checkpoint inhibition in advanced gastroesophageal cancer: systematic review and meta-analysis of 17 phase 3 randomized clinical trials. JAMA Oncol, 2022, 8(10): 1456-1465.
37. Li JB, Lai MY, Lin ZC, et al. The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis. Cancer Immunol Immunother, 2024, 73(7): 132. doi: 10.1007/s00262-024-03726-1.
38. Huang C, Ren S, Chen Y, et al. PD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance. Sci Adv, 2023, 9(21): eade4186. 10.1126/sciadv. ade4186.
39. Komori A, Hironaka S, Kadowaki S, et al. Prevalence and clinicopathological features of microsatellite instability-high metastatic or recurrent gastric and esophagogastric junction cancer: WJOG13320GPS. Gastric Cancer, 2025, 28(2): 301-308.
40. Ooki A, Osumi H, Yoshino K, et al. Potent therapeutic strategy in gastric cancer with microsatellite instability-high and/or deficient mismatch repair. Gastric Cancer, 2024, 27(5): 907-931.
41. Landre T, Des Guetz G. Microsatellite instability-high status as a pan-cancer biomarker for immunotherapy efficacy. Cancer Immunol Immunother, 2025, 74(4): 122. doi: 10.1007/s00262-025-03980-x.
42. Ke L, Li S, Huang D. The predictive value of tumor mutation burden on survival of gastric cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Int Immunopharmacol, 2023, 124(Pt B): 110986. doi: 10.1016/j.intimp.2023.110986.
43. Lee KW, Van Cutsem E, Bang YJ, et al. Association of tumor mutational burden with efficacy of pembrolizumab±chemotherapy as first-line therapy for gastric cancer in the phase III KEYNOTE-062 study. Clin Cancer Res, 2022, 28(16): 3489-3498.
44. Wang J, Xiu J, Farrell A, et al. Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study. Lancet Oncol, 2023, 24(2): 151-161.
45. Yee EJ, Gilbert D, Kaplan J, et al. Immune landscape of Epstein-Barr Virus-associated gastric cancer: analysis from a western academic institution. J Surg Res, 2024, 296: 742-750.
46. Kondo A, Shinozaki-Ushiku A, Rokutan H, et al. Loss of viral genome with altered immune microenvironment during tumour progression of Epstein-Barr virus-associated gastric carcinoma. J Pathol, 2023, 260(2): 124-136.
47. Li LL, Yu AY, Zhu M, et al. Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer. Arch Virol, 2024, 169(5): 114. doi: 10.1007/s00705-024-06033-3.
48. Xie T, Liu Y, Zhang Z, et al. Positive status of Epstein-Barr Virus as a biomarker for gastric cancer immunotherapy: a prospective observational study. J Immunother, 2020, 43(4): 139-144.
49. Bai Y, Xie T, Wang Z, et al. Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer. J Immunother Cancer, 2022, 10(3): e004080. doi: 10.1136/jitc-2021-004080.
50. Ziogou A, Giannakodimos A, Giannakodimos I, et al. Effect of helicobacter pylori infection on immunotherapy for gastrointestinal cancer: a narrative review. Immunotherapy, 2025, 17(5): 355-368.
51. Jia K, Chen Y, Xie Y, et al. Helicobacter pylori and immunotherapy for gastrointestinal cancer. Innovation (Camb), 2024, 5(2): 100561. doi: 10.1016/j.xinn.2023.100561.
52. Gong X, Shen L, Xie J, et al. Helicobacter pylori infection reduces the efficacy of cancer immunotherapy: A systematic review and meta-analysis. Helicobacter, 2023, 28(6): e13011. doi: 10.1111/hel.13011.
53. Yu B, Peppelenbosch M, Fuhler G. Impact of helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J Immunother Cancer, 2024, 12(1): e008422. doi: 10.1136/jitc-2023-008422.
54. Yu B, Peppelenbosch M, Fuhler G. Impact of helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J Immunother Cancer, 2024, 12(1): e008422. doi: 10.1136/jitc-2023-008422.
55. Verschoor YL, van de Haar J, van den Berg JG, et al. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med, 2024, 30(2): 519-530.
56. Yin J, Yuan J, Li Y, et al. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med, 2023, 29(8): 2068-2078.
57. Chen X, Xu H, Chen X, et al. First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study. Signal Transduct Target Ther, 2024, 9(1): 73. doi: 10.1038/s41392-024-01773-9.
58. Fagery M, Khorshidi HA, Wong SQ, et al. Health economic evidence and modeling challenges for liquid biopsy assays in cancer management: a systematic literature review. Pharmacoeconomics, 2023, 41(10): 1229-1248.
59. Zhang Z, Wu H, Chong W, et al. Liquid biopsy in gastric cancer: predictive and prognostic biomarkers. Cell Death Dis, 2022, 13(10): 903. doi: 10.1038/s41419-022-05350-2.
60. Zhang H, Jin T, Peng Y, et al. Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis. Int J Surg, 2024, 110(7): 4370-4381.
61. Min L, Chen J, Yu M, et al. Utilizing circulating tumour DNA as a prognostic predictor of gastric cancer: a meta-analysis. Biomarkers, 2023, 28(5): 427-436.
62. Cui Q, Li W, Wang D, et al. Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis. World J Surg Oncol, 2023, 21(1): 318. doi: 10.1186/s12957-023-03215-2.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest ArticlesResearch progress on ICIs therapy for gastric cancer and biomarkers for predicting therapeutic efficacy

Abstract Full text Figures/Tables Video References Cited by

Format

Content