肿瘤微环境中T细胞功能障碍及其逆转策略

Dysfunction of T cell in tumor microenvironment and strategy of reversing the dysfunction

肿瘤微环境中T细胞功能障碍是肿瘤逃逸免疫监视的关键机制,免疫检查点分子上调导致的T细胞功能障碍是目前的研究热点。阻断免疫检查点PD-1和CTLA-4的临床试验在许多晚期癌症患者中显示令人鼓舞的疗效,证实肿瘤微环境中存在T细胞功能障碍以及逆转T细胞功能障碍在肿瘤治疗中的潜力。然而,这些新的免疫治疗方法只在少数癌症患者中产生持久的临床疗效,提示肿瘤微环境的异质性和复杂性。最近,单细胞水平的研究进一步阐明了肿瘤微环境中T细胞功能障碍的表型特征和临床意义,揭示表观遗传学和代谢改变是导致肿瘤微环境中T细胞功能障碍的重要机制,并提出逆转肿瘤微环境T细胞功能障碍的新方法。本文聚焦这些肿瘤微环境中T细胞功能障碍及其逆转策略的最新研究进展。

T cell dysfunction in tumor microenvironment is the key mechanism of tumor escaping from immune surveillance. T cell dysfunction induced by up-regulating expression of immune checkpoint molecules is a hot point of the current research. The clinical trials of blocking immune checkpoint, PD-1 and CTLA-1, have shown encourag- ing efficacy in the many patients with advanced cancer. It was confirmed that there was T cell dysfunction in tumor microenvironment and reversing T cell dysfunction could play a potentiality in tumor therapy. However, the novel immunotherapy methods exhibited a long-lasting clinical efficacy in a small number of the patients with cancer on- ly, which suggest heterogeneity and complexity of the tumor microenvironment. Recently, the research in unicellular level further clarified phenotypic characteristics and clinical significance of T cell dysfunction in tumor microenvi- ronment, which reveals that epigenetics and metabolic changes are the important mechanisms resulting in T cell dys- function in the tumor microenvironment and suggests the novel methods for reversing T cell dysfunction in the tu- mor microenvironment. This paper focus on the latest research progresses of the T cell dysfunction in the tumor mi- croenvironment and strategy of reversing the T cell dysfunction.