晚期胃癌免疫治疗研究进展
Research Progress of Immunotherapy in Advanced Gastric Cancer
DOI: 10.12677/jcpm.2026.54286, PDF,   
作者: 杨 洋, 姚静娴, 张 慧：承德医学院研究生学院，河北 承德；代俊利, 孙同友*：承德市中心医院肿瘤放化疗中心，河北 承德
关键词: 免疫治疗；晚期胃癌；免疫检查点抑制剂；Immunotherapy； Advanced Gastric Cancer； Immune Checkpoint Inhibitors
摘要: 绝大多数胃癌患者在确诊时已处于进展期或晚期，不仅失去手术治疗的机会，常规的化疗也面临着不良反应多、疗效差等多种情况。免疫治疗作为近年来的研究热点，已逐渐展现出它不可替代的优势。免疫检查点抑制剂已在晚期胃癌中发挥出举足轻重的作用，同时，许多新兴免疫检查点的探索及治疗策略的创新，也为免疫治疗带来了新的希望，相信在不久的将来，免疫治疗将为晚期胃癌带来前所未有的革新。
Abstract: The vast majority of gastric cancer patients are already in the progressive or advanced stage when they are diagnosed, not only losing the opportunity of surgical treatment, but also facing many adverse reactions and poor efficacy of conventional chemotherapy. As a research hotspot in recent years, immunotherapy has gradually shown its irreplaceable advantages. Immune checkpoint inhibitors have already played a pivotal role in advanced gastric cancer, meanwhile, the exploration of many emerging immune checkpoints and the innovation of therapeutic strategies have also added a colorful touch to immunotherapy, and it is believed that immunotherapy will bring unprecedented innovation to advanced gastric cancer in the near future.
文章引用：杨洋, 姚静娴, 张慧, 代俊利, 孙同友. 晚期胃癌免疫治疗研究进展[J]. 临床个性化医学, 2026, 5(4): 590-599. https://doi.org/10.12677/jcpm.2026.54286

参考文献

[1] Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., et al. (2024) Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74, 229-263.
https://doi.org/10.3322/caac.21834
[2] 王雯雯, 刘文斌, 曹广文. 胃癌发病性别差异的相关危险因素[J]. 上海预防医学, 2017, 29(4): 257-260, 284.
[3] 任闪闪, 姬发祥. 晚期胃癌免疫治疗的现状[J]. 临床个性化医学, 2024, 3(2): 328-334.
[4] Moehler, M., Xiao, H., Blum, S.I., et al. (2023) Health-Related Quality of Life with Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients with Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma from CheckMate 649. Journal of Clinical Oncology, 41, 5388-5399.
[5] 刘怡璘, 张小田. 免疫检查点抑制剂在胃癌治疗中的研究进展[J]. 中华消化外科杂志, 2019, 18(5): 509-512.
[6] Zhang, X., Wang, J., Wang, G., Zhang, Y., Fan, Q., Chuangxin, L., et al. (2023) LBA79 GEMSTONE-303: Prespecified Progression-Free Survival (PFS) and Overall Survival (OS) Final Analyses of a Phase III Study of Sugemalimab Plus Chemotherapy vs Placebo Plus Chemotherapy in Treatment-Naïve Advanced Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma. Annals of Oncology, 34, S1319.
https://doi.org/10.1016/j.annonc.2023.10.080
[7] Chen, X., Wang, S., Chen, Y., Xin, H., Zhang, S., Wu, D., et al. (2023) Non-Invasive Activation of Intratumoural Gene Editing for Improved Adoptive T-Cell Therapy in Solid Tumours. Nature Nanotechnology, 18, 933-944.
https://doi.org/10.1038/s41565-023-01378-3
[8] Zhou, X., Wang, Y., Dou, Z., Delfanti, G., Tsahouridis, O., Pellegry, C.M., et al. (2024) Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity to CAR-T Cells through Multimodal CD1d-Dependent Mechanisms. Nature Cancer, 5, 1607-1621.
https://doi.org/10.1038/s43018-024-00830-0
[9] Martinez Bedoya, D., Marinari, E., Davanture, S., Castillo Cantero, L., et al. (2024) PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma. Cancer Immunology Research, 12, 1718-1735.
[10] Qi, C., Gong, J., Li, J., Liu, D., Qin, Y., Ge, S., et al. (2022) Claudin18.2-Specific CAR T Cells in Gastrointestinal Cancers: Phase 1 Trial Interim Results. Nature Medicine, 28, 1189-1198.
https://doi.org/10.1038/s41591-022-01800-8
[11] Tobias, J., Maglakelidze, M., Andrić, Z., Ryspayeva, D., Bulat, I., Nikolić, I., et al. (2024) Phase II Trial of HER-Vaxx, a B-Cell Peptide-Based Vaccine, in HER2-Overexpressing Advanced Gastric Cancer Patients under Platinum-Based Chemotherapy (Herizon). Clinical Cancer Research, 30, 4044-4054.
https://doi.org/10.1158/1078-0432.ccr-24-0742
[12] Guo, Z., Yuan, Y., Chen, C., Lin, J., Ma, Q., Liu, G., et al. (2022) Durable Complete Response to Neoantigen-Loaded Dendritic-Cell Vaccine Following Anti-Pd-1 Therapy in Metastatic Gastric Cancer. npj Precision Oncology, 6, Article No. 22.
https://doi.org/10.1038/s41698-022-00279-3
[13] Shitara, K., Van Cutsem, E., Bang, Y., Fuchs, C., Wyrwicz, L., Lee, K., et al. (2020) Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients with First-Line, Advanced Gastric Cancer. JAMA Oncology, 6, 1571-1580.
https://doi.org/10.1001/jamaoncol.2020.3370
[14] Janjigian, Y.Y., Shitara, K., Moehler, M., Garrido, M., Salman, P., Shen, L., et al. (2021) 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. The Lancet, 398, 27-40.
https://doi.org/10.1016/s0140-6736(21)00797-2
[15] Kang, Y.K., Chen, L., Ryu, M., Oh, D., Oh, S.C., Chung, H.C., et al. (2022) 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. The Lancet Oncology, 23, 234-247.
https://doi.org/10.1016/s1470-2045(21)00692-6
[16] Rha, S.Y., Wyrwicz, L.S., Weber, P.E.Y., Bai, Y., Ryu, M.H., Lee, J., et al. (2023) VP1-2023: Pembrolizumab (Pembro) Plus Chemotherapy (Chemo) as First-Line Therapy for Advanced HER2-Negative Gastric or Gastroesophageal Junction (G/GEJ) Cancer: Phase III KEYNOTE-859 Study. Annals of Oncology, 34, 319-320.
https://doi.org/10.1016/j.annonc.2023.01.006
[17] Xu, J., Jiang, H., Pan, Y., Gu, K., Cang, S., Han, L., Shu, Y., et al. (2023) Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial. JAMA, 330, 2064-2074.
[18] Shitara, K., Özgüroğlu, M., Bang, Y., Di Bartolomeo, M., Mandalà, M., Ryu, M., et al. (2018) Pembrolizumab versus Paclitaxel for Previously Treated, Advanced Gastric or Gastro-Oesophageal Junction Cancer (KEYNOTE-061): A Randomised, Open-Label, Controlled, Phase 3 Trial. The Lancet, 392, 123-133.
https://doi.org/10.1016/s0140-6736(18)31257-1
[19] Fuchs, C.S., Doi, T., Jang, R.W., Muro, K., Satoh, T., Machado, M., et al. (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 Oncology, 15, e180013.
[20] Kang, Y.K., Boku, N., Satoh, T., Ryu, M.H., Chao, Y., Kato, K., Chung, H.C., Chen, J.S., et al. (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. The Lancet, 390, 2461-2471.
[21] Chung, H., Bang, Y., Fuchs, C., Qin, S., Satoh, T., Shitara, K., et al. (2019) KEYNOTE-811 Pembrolizumab Plus Trastuzumab and Chemotherapy for HER2+ Metastatic Gastric or Gastroesophageal Junction Cancer: A Double-Blind, Randomized, Placebo-Controlled Phase 3 Study. Annals of Oncology, 30, v1038-v1039.
https://doi.org/10.1093/annonc/mdz155.093
[22] Gong, J., Chen, L., Sun, M., Ni, M., Zhao, R., Wang, X., et al. (2023) Efficacy and Safety of KN026 in Combination with KN046 in Patients with Locally Advanced Unresectable or Metastatic HER2-Positive Other Solid Tumors. Journal of Clinical Oncology, 41, 3621-3621.
https://doi.org/10.1200/jco.2023.41.16_suppl.3621
[23] Hsu, C.-H., Lu, Z., Gao, S. and Wang, J.-Y. (2024) SKYSCRAPER-08: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of First-Line (1L) Tiragolumab (Tira) + Atezolizumab (Atezo) and Chemotherapy (CT) in Patients (PTS) with Esophageal Squamous Cell Carcinoma (ESCC). Journal of Clinical Oncology, 42, 245-245.
[24] Harding, J.J., Moreno, V., Bang, Y., Hong, M.H., Patnaik, A., Trigo, J., et al. (2021) Blocking TIM-3 in Treatment-Refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-Pd-L1 Antibody. Clinical Cancer Research, 27, 2168-2178.
https://doi.org/10.1158/1078-0432.ccr-20-4405
[25] Roche, H.-L. (2021) A 3-Arm, Randomized, Blinded, Active-Controlled, Phase II Study of RO7121661, a PD1-TIM3 Bispecific Antibody and RO7247669, a PD1-LAG3 Bispecific Antibody, Compared with Nivolumab in Participants with Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus. ClinicalTrials.gov Identifier: NCT04785820.
https://clinicaltrials.gov/ct2/show/NCT04785820
[26] Ji, J., Shen, L., Gao, X., Ji, K., Chen, Y., Xu, N., et al. (2022) A Phase Ib/II, Multicenter, Open-Label Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined with Chemotherapy (Chemo) as First-Line Therapy for Advanced Gastric (G) or Gastroesophageal Junction (GEJ) Cancer. Journal of Clinical Oncology, 40, 308-308.
https://doi.org/10.1200/jco.2022.40.4_suppl.308