Hematology and Medical Oncology, Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
WWAMI School of Medical Education, University of Alaska Anchorage, Anchorage, AK, USA.
Cancer Gene Ther. 2021 Sep;28(9):924-934. doi: 10.1038/s41417-021-00310-y. Epub 2021 Mar 4.
Gastric cancer (GC) is an aggressive malignancy that is the third leading cause of cancer mortality worldwide. Localized GC can be cured with surgery, but most patients present with more advanced non-operable disease. Until recently, treatment options for relapsed and refractory advanced GC have been limited to combination chemotherapy regimens, HER-2 directed therapy, and radiation, which lead to few durable responses. Over the past decade, there have been significant advances in our understanding of the molecular and immune pathogenesis of GC. The infectious agents Epstein-Barr virus and Helicobacter pylori perturb the gastric mucosa immune equilibrium, which creates a microenvironment that favors GC tumorigenesis and evasion of immune surveillance. Insights into immune mechanisms of GC have translated into novel therapeutics, including immune checkpoint inhibitors, which have become a treatment option for select patients with GC. Furthermore, chimeric antigen receptor T-cell therapies have emerged as a breakthrough treatment for many cancers, with recent studies showing this to be a potential therapy for GC. In this review, we summarize the current state of knowledge on immune mechanisms of GC and the status of emerging immunotherapies to treat this aggressive cancer, as well as outline current challenges and directions for future research.
胃癌(GC)是一种侵袭性恶性肿瘤,是全球癌症死亡的第三大主要原因。局部 GC 可以通过手术治愈,但大多数患者表现出更晚期的不可手术疾病。直到最近,复发性和难治性晚期 GC 的治疗选择一直局限于联合化疗方案、HER-2 定向治疗和放疗,这些治疗方法导致很少有持久的反应。在过去的十年中,我们对 GC 的分子和免疫发病机制的理解取得了重大进展。传染性病原体 Epstein-Barr 病毒和 Helicobacter pylori 扰乱了胃黏膜的免疫平衡,创造了有利于 GC 肿瘤发生和逃避免疫监视的微环境。对 GC 免疫机制的深入了解已经转化为新的治疗方法,包括免疫检查点抑制剂,这已成为 GC 患者的一种治疗选择。此外,嵌合抗原受体 T 细胞疗法已成为许多癌症的突破性治疗方法,最近的研究表明,这可能是 GC 的一种潜在治疗方法。在这篇综述中,我们总结了 GC 的免疫机制的现有知识状况以及新兴免疫疗法治疗这种侵袭性癌症的现状,并概述了当前的挑战和未来研究的方向。