Immunotherapy for gastric cancer: Advances and challenges

Pei Zhang, Chenyan Zhang, Xiaoying Li, Chen Chang, Cailing Gan, Tinghong Ye, Dan Cao
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Abstract

Gastric cancer (GC) ranks among the leading causes of cancer-related mortality globally. Often, its initial stages manifest subtly, and the infrequency of routine screenings contributes to late diagnoses in many cases. Systemic treatments for GC include chemotherapy, targeted therapy, and immunotherapy, among which immunotherapy is the first-line standard treatment for advanced GC. In recent years, immunotherapy has seen notable advancements, as evidenced by the Food and Drug Administration's approval of drugs such as nivolumab and pembrolizumab for GC treatment. Additionally, several other drugs are currently under rigorous preclinical and clinical investigation. This review aims to shed light on the recent advancements in immunotherapy for GC, particularly emphasizing the insights gained from phase 2/3 clinical trials that assess the efficacy, safety, and promise of various immunotherapeutic modalities, including immune checkpoint inhibitors, CAR-T-cell therapies, and cancer vaccines, in enhancing patient outcomes. Moreover, this review delves into the intricate immunological framework of GC, focusing on the tumor microenvironment, interactions among immune cells, and the roles of immune checkpoints such as PD-L1. We also address the hurdles and prospective paths forward in the realm of immunotherapy for GC, offering fresh viewpoints on potential therapeutic approaches in this evolving domain.

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胃癌免疫疗法:进展与挑战
胃癌(GC)是全球癌症相关死亡的主要原因之一。胃癌的初期症状往往很不明显,而常规筛查又不常见,导致很多病例诊断较晚。GC 的系统治疗包括化疗、靶向治疗和免疫治疗,其中免疫治疗是晚期 GC 的一线标准治疗方法。近年来,免疫疗法取得了显著进展,美国食品和药物管理局已批准 nivolumab 和 pembrolizumab 等药物用于 GC 治疗。此外,目前还有其他几种药物正在接受严格的临床前和临床研究。本综述旨在阐明 GC 免疫疗法的最新进展,特别强调从 2/3 期临床试验中获得的见解,这些临床试验评估了各种免疫治疗模式(包括免疫检查点抑制剂、CAR-T 细胞疗法和癌症疫苗)的疗效、安全性和前景,以提高患者的预后。此外,本综述还深入探讨了 GC 错综复杂的免疫学框架,重点关注肿瘤微环境、免疫细胞之间的相互作用以及 PD-L1 等免疫检查点的作用。我们还探讨了 GC 免疫疗法领域的障碍和前景,为这一不断发展的领域中的潜在治疗方法提供了新的观点。
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