The Royal Marsden Hospital NHS Foundation Trust, London and Sutton, UK.
Institute of Cancer Research, Sutton, UK.
Cancer Treat Res. 2024;192:277-303. doi: 10.1007/978-3-031-61238-1_14.
Immunotherapy has revolutionised cancer treatment over the past decade. Long-term durable responses can be achieved in some cancer patient populations that were previously facing terminal disease. In this chapter, we summarise current phase 3 clinical trial evidence for the use of immunotherapy in gastrointestinal cancers (oesophageal squamous cell carcinoma, oesophago-gastric adenocarcinoma, pancreatic cancer, biliary cancer, hepatocellular carcinoma, colorectal cancer, and squamous cell cancer of the anus). We discuss meaningful biomarkers used in clinical trials to select patients most likely to benefit from immunotherapy, such as mismatch-repair deficiency (MMRd)/microsatellite instability (MSI) and programmed-death-ligand-1 (PD-L1) immunohistochemistry (IHC) expression. Clinical questions are arising regarding the role of immunotherapy in the adjuvant/perioperative setting, optimal timing of surgery in patients who respond to immunotherapy, and toxicities specific to patients with gastrointestinal malignancies. We outline the current landscape and future horizon of immunotherapy in gastrointestinal cancers, such as strategies to increase effectiveness of checkpoint blockade through combinations with other checkpoint inhibitors, cytotoxic chemotherapy, targeted agents, radiotherapy, CAR-T therapy, and cancer vaccines.
免疫疗法在过去十年中彻底改变了癌症治疗。在一些以前面临绝症的癌症患者群体中，可以实现长期持久的应答。在本章中，我们总结了免疫疗法在胃肠道癌症（食管鳞状细胞癌、食管胃腺癌、胰腺癌、胆管癌、肝细胞癌、结直肠癌和肛门鳞状细胞癌）中的当前 3 期临床试验证据。我们讨论了在临床试验中用于选择最有可能从免疫疗法中获益的患者的有意义的生物标志物，例如错配修复缺陷（MMRd）/微卫星不稳定性（MSI）和程序性死亡配体-1（PD-L1）免疫组化（IHC）表达。关于免疫疗法在辅助/围手术期的作用、对免疫疗法有反应的患者手术的最佳时机以及胃肠道恶性肿瘤患者特有的毒性等临床问题正在出现。我们概述了胃肠道癌症免疫疗法的当前现状和未来前景，例如通过与其他检查点抑制剂、细胞毒性化疗、靶向药物、放疗、CAR-T 疗法和癌症疫苗联合使用来提高检查点阻断的效果的策略。
