Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
The Second Clinical Medicine School, Nanchang University, Nanchang, China.
Front Immunol. 2023 Apr 25;14:1149622. doi: 10.3389/fimmu.2023.1149622. eCollection 2023.
CD8 T cells, a cytotoxic T lymphocyte, are a key component of the tumor immune system, but they enter a hyporeactive T cell state in long-term chronic inflammation, and how to rescue this depleted state is a key direction of research. Current studies on CD8 T cell exhaustion have found that the mechanisms responsible for their heterogeneity and differential kinetics may be closely related to transcription factors and epigenetic regulation, which may serve as biomarkers and potential immunotherapeutic targets to guide treatment. Although the importance of T cell exhaustion in tumor immunotherapy cannot be overstated, studies have pointed out that gastric cancer tissues have a better anti-tumor T cell composition compared to other cancer tissues, which may indicate that gastrointestinal cancers have more promising prospects for the development of precision-targeted immunotherapy. Therefore, the present study will focus on the mechanisms involved in the development of CD8 T cell exhaustion, and then review the landscapes and mechanisms of T cell exhaustion in gastrointestinal cancer as well as clinical applications, which will provide a clear vision for the development of future immunotherapies.
CD8 T 细胞，即细胞毒性 T 淋巴细胞，是肿瘤免疫系统的关键组成部分，但在长期慢性炎症中，它们会进入低反应性 T 细胞状态，如何挽救这种耗竭状态是研究的关键方向。目前对 CD8 T 细胞耗竭的研究发现，导致其异质性和差异动力学的机制可能与转录因子和表观遗传调控密切相关，这些可能作为生物标志物和潜在的免疫治疗靶点，以指导治疗。尽管 T 细胞耗竭在肿瘤免疫治疗中的重要性不言而喻，但研究指出，与其他癌症组织相比，胃癌组织具有更好的抗肿瘤 T 细胞组成，这可能表明胃肠道癌症在开发精准靶向免疫治疗方面具有更广阔的前景。因此，本研究将重点关注 CD8 T 细胞耗竭的发展机制，然后综述胃肠道癌症中 T 细胞耗竭的景观和机制及其临床应用，为未来免疫疗法的发展提供清晰的前景。
