免疫治疗在胃癌伴肝转移中的应用
Application of Immunotherapy in Gastric Cancer with Liver Metastasis
DOI: 10.12677/acm.2025.152361, PDF,   
作者: 谢欣宇:延安大学医学院,陕西 延安;延安大学附属医院胃肠疝外科,陕西 延安;雷 星*:延安大学附属医院胃肠疝外科,陕西 延安
关键词: 胃癌免疫疗法肝转移转移性胃癌Gastric Cancer Immunotherapy Liver Metastasis Metastatic Gastric Cancer
摘要: 胃癌依然是一个重大的公共卫生挑战,其特征为高发病率和高死亡率。肝脏是胃癌转移的主要靶器官,而腹膜、肺部和骨骼也是常见的转移部位。随着生物疗法的引入以及免疫治疗在转移性胃癌治疗中的应用,针对该病的治疗选择已显著增加。这些多样化的治疗方法均旨在改善患者的生活质量并延长生存期,体现了胃癌及其肝转移治疗领域的进展。这篇论文的意义在于关注了肝转移对胃癌免疫治疗效果的影响,这是一个临床上重要且亟待解决的问题。目前关于免疫疗法在胃癌中的研究较多,但专门针对肝转移患者的研究相对较少。该研究试图填补这一空白,并为临床决策提供参考。
Abstract: Gastric cancer continues to pose a significant public health challenge, marked by high incidence and mortality rates. The liver is the predominant organ for gastric cancer metastasis, while the peritoneum, lung, and bone are also frequent sites of metastatic spread. The advent of biotherapy and the incorporation of immunotherapy in treating metastatic gastric cancer have substantially expanded therapeutic options. These treatments aim to enhance patient quality of life and extend survival, reflecting advancements in the management of gastric cancer and its hepatic metastases. This paper’s significance lies in its focus on how liver metastasis influences the efficacy of immunotherapy in gastric cancer, an issue that is both clinically important and urgent. Although numerous studies have explored immunotherapy in gastric cancer, relatively few have specifically addressed patients with liver metastasis. This study seeks to address this gap and inform clinical decision-making.
文章引用:谢欣宇, 雷星. 免疫治疗在胃癌伴肝转移中的应用[J]. 临床医学进展, 2025, 15(2): 414-420. https://doi.org/10.12677/acm.2025.152361

参考文献

[1] Rawla, P. and Barsouk, A. (2019) Epidemiology of Gastric Cancer: Global Trends, Risk Factors and Prevention. Gastroenterology Review, 14, 26-38. [Google Scholar] [CrossRef] [PubMed]
[2] 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. [Google Scholar] [CrossRef] [PubMed]
[3] Oki, E., Tokunaga, S., Emi, Y., Kusumoto, T., Yamamoto, M., Fukuzawa, K., et al. (2015) Surgical Treatment of Liver Metastasis of Gastric Cancer: A Retrospective Multicenter Cohort Study (KSCC1302). Gastric Cancer, 19, 968-976. [Google Scholar] [CrossRef] [PubMed]
[4] Shasha, T., Gruijs, M. and van Egmond, M. (2022) Mechanisms of Colorectal Liver Metastasis Development. Cellular and Molecular Life Sciences, 79, Article 607. [Google Scholar] [CrossRef] [PubMed]
[5] Wu, K., Zhang, G., Shen, C., Zhu, L., Yu, C., Sartorius, K., et al. (2024) Role of T Cells in Liver Metastasis. Cell Death & Disease, 15, Article 341. [Google Scholar] [CrossRef] [PubMed]
[6] Ghorani, E., Swanton, C. and Quezada, S.A. (2023) Cancer Cell-Intrinsic Mechanisms Driving Acquired Immune Tolerance. Immunity, 56, 2270-2295. [Google Scholar] [CrossRef] [PubMed]
[7] Sordo-Bahamonde, C., Lorenzo-Herrero, S., Gonzalez-Rodriguez, A.P., Martínez-Pérez, A., Rodrigo, J.P., García-Pedrero, J.M., et al. (2023) Chemo-Immunotherapy: A New Trend in Cancer Treatment. Cancers, 15, Article 2912. [Google Scholar] [CrossRef] [PubMed]
[8] Zhang, Z., Liu, X., Chen, D. and Yu, J. (2022) Radiotherapy Combined with Immunotherapy: The Dawn of Cancer Treatment. Signal Transduction and Targeted Therapy, 7, Article No. 258. [Google Scholar] [CrossRef] [PubMed]
[9] Bang, Y., Van Cutsem, E., Feyereislova, A., Chung, H.C., Shen, L., Sawaki, A., et al. (2010) Trastuzumab in Combination with Chemotherapy versus Chemotherapy Alone for Treatment of Her2-Positive Advanced Gastric or Gastro-Oesophageal Junction Cancer (Toga): A Phase 3, Open-Label, Randomised Controlled Trial. The Lancet, 376, 687-697. [Google Scholar] [CrossRef] [PubMed]
[10] Janjigian, Y.Y., Kawazoe, A., Bai, Y., Xu, J., Lonardi, S., Metges, J.P., et al. (2023) 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. The Lancet, 402, 2197-2208. [Google Scholar] [CrossRef] [PubMed]
[11] Kang, Y., 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. [Google Scholar] [CrossRef] [PubMed]
[12] Rha, S.Y., Oh, D., Yañez, P., Bai, Y., Ryu, M., Lee, J., et al. (2023) Pembrolizumab Plus Chemotherapy versus Placebo Plus Chemotherapy for Her2-Negative Advanced Gastric Cancer (KEYNOTE-859): A Multicentre, Randomised, Double-Blind, Phase 3 Trial. The Lancet Oncology, 24, 1181-1195. [Google Scholar] [CrossRef] [PubMed]
[13] Le, D.T., Durham, J.N., Smith, K.N., Wang, H., Bartlett, B.R., Aulakh, L.K., et al. (2017) Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade. Science, 357, 409-413. [Google Scholar] [CrossRef] [PubMed]
[14] Makker, V., Colombo, N., Casado Herráez, A., Santin, A.D., Colomba, E., Miller, D.S., et al. (2022) Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer. New England Journal of Medicine, 386, 437-448. [Google Scholar] [CrossRef] [PubMed]
[15] Kole, C., Charalampakis, N., Tsakatikas, S., Kouris, N., Papaxoinis, G., Karamouzis, M.V., et al. (2021) Immunotherapy for Gastric Cancer: A 2021 Update. Immunotherapy, 14, 41-64. [Google Scholar] [CrossRef] [PubMed]
[16] Muro, K., Chung, H.C., Shankaran, V., Geva, R., Catenacci, D., Gupta, S., et al. (2016) Pembrolizumab for Patients with Pd-L1-Positive Advanced Gastric Cancer (KEYNOTE-012): A Multi-Centre, Open-Label, Phase 1b Trial. The Lancet Oncology, 17, 717-726. [Google Scholar] [CrossRef] [PubMed]
[17] 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. JAMA Oncology, 4, e180013. [Google Scholar] [CrossRef] [PubMed]
[18] Fuchs, C.S., Özgüroğlu, M., Bang, Y., Di Bartolomeo, M., Mandala, M., Ryu, M., et al. (2021) Pembrolizumab versus Paclitaxel for Previously Treated Pd-L1-Positive Advanced Gastric or Gastroesophageal Junction Cancer: 2-Year Update of the Randomized Phase 3 KEYNOTE-061 Trial. Gastric Cancer, 25, 197-206. [Google Scholar] [CrossRef
[19] 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, Article 1571. [Google Scholar] [CrossRef] [PubMed]
[20] Janjigian, Y.Y., Bendell, J., Calvo, E., Kim, J.W., Ascierto, P.A., Sharma, P., et al. (2018) Checkmate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients with Metastatic Esophagogastric Cancer. Journal of Clinical Oncology, 36, 2836-2844. [Google Scholar] [CrossRef] [PubMed]
[21] André, T., Berton, D., Curigliano, G., Sabatier, R., Tinker, A.V., Oaknin, A., et al. (2023) Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients with Mismatch Repair Deficient Solid Tumors. JAMA Network Open, 6, e2341165. [Google Scholar] [CrossRef] [PubMed]
[22] Hou, W., Zhao, Y. and Zhu, H. (2023) Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects. International Journal of Molecular Sciences, 24, Article 15321. [Google Scholar] [CrossRef] [PubMed]
[23] Hu, H., Tsai, H., Ku, H., Lo, S., Shan, Y., Chang, H., et al. (2021) Survival Outcomes of Management in Metastatic Gastric Adenocarcinoma Patients. Scientific Reports, 11, Article No. 23142. [Google Scholar] [CrossRef] [PubMed]
[24] Kroese, T.E., van Laarhoven, H.W.M., Schoppman, S.F., Deseyne, P.R.A.J., van Cutsem, E., Haustermans, K., et al. (2023) Definition, Diagnosis and Treatment of Oligometastatic Oesophagogastric Cancer: A Delphi Consensus Study in Europe. European Journal of Cancer, 185, 28-39. [Google Scholar] [CrossRef] [PubMed]
[25] Zhang, P., Shi, X. and Li, Q. (2023) Nivolumab Plus Chemotherapy versus Chemotherapy Alone as First-Line Treatment for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Cost-Effectiveness Analysis. Cost Effectiveness and Resource Allocation, 21, Article No. 65. [Google Scholar] [CrossRef] [PubMed]
[26] Fukuoka, S., Hara, H., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M., et al. (2020) Regorafenib Plus Nivolumab in Patients with Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, Epoc1603). Journal of Clinical Oncology, 38, 2053-2061. [Google Scholar] [CrossRef] [PubMed]
[27] Raskov, H., Orhan, A., Christensen, J.P. and Gögenur, I. (2020) Cytotoxic CD8+ T Cells in Cancer and Cancer Immunotherapy. British Journal of Cancer, 124, 359-367. [Google Scholar] [CrossRef] [PubMed]
[28] Durgeau, A., Virk, Y., Corgnac, S. and Mami-Chouaib, F. (2018) Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy. Frontiers in Immunology, 9, Article 14. [Google Scholar] [CrossRef] [PubMed]
[29] Yu, J., Green, M.D., Li, S., Sun, Y., Journey, S.N., Choi, J.E., et al. (2021) Liver Metastasis Restrains Immunotherapy Efficacy via Macrophage-Mediated T Cell Elimination. Nature Medicine, 27, 152-164. [Google Scholar] [CrossRef] [PubMed]
[30] Deng, J., Gou, Q., Yang, L., Chen, Z., Yang, M., Yang, X., et al. (2023) Immune Suppressive Microenvironment in Liver Metastases Contributes to Organ-Specific Response of Immunotherapy in Advanced Non-Small Cell Lung Cancer. Journal for ImmunoTherapy of Cancer, 11, e007218. [Google Scholar] [CrossRef] [PubMed]
[31] Liu, K., Wu, C., Liang, H., Wang, T., Zhang, J. and Wang, X. (2024) Analysis of the Impact of Immunotherapy Efficacy and Safety in Patients with Gastric Cancer and Liver Metastasis. World Journal of Gastrointestinal Surgery, 16, 700-709. [Google Scholar] [CrossRef] [PubMed]
[32] Entezam, M., Sanaei, M., Mirzaei, Y., Mer, A.H., Abdollahpour-Alitappeh, M., Azadegan-Dehkordi, F., et al. (2023) Current Progress and Challenges of Immunotherapy in Gastric Cancer: A Focus on CAR-T Cells Therapeutic Approach. Life Sciences, 318, Article 121459. [Google Scholar] [CrossRef] [PubMed]
[33] Bębnowska, D., Grywalska, E., Niedźwiedzka-Rystwej, P., Sosnowska-Pasiarska, B., Smok-Kalwat, J., Pasiarski, M., et al. (2020) CAR-T Cell Therapy—An Overview of Targets in Gastric Cancer. Journal of Clinical Medicine, 9, Article 1894. [Google Scholar] [CrossRef] [PubMed]
[34] Budi, H.S., Ahmad, F.N., Achmad, H., Ansari, M.J., Mikhailova, M.V., Suksatan, W., et al. (2022) Human Epidermal Growth Factor Receptor 2 (HER2)-Specific Chimeric Antigen Receptor (CAR) for Tumor Immunotherapy; Recent Progress. Stem Cell Research & Therapy, 13, Article No. 40. [Google Scholar] [CrossRef] [PubMed]