CD8+ T 细胞是抗肿瘤免疫应答的主要执行者。通过重塑CD8+ T 细胞杀伤肿瘤细胞的能力，免疫疗法已在抗肿瘤领域取得重大突破，但临床获益仅局限于部分患者和癌症类型。如何克服CD8+ T细胞功能障碍是肿瘤免疫疗法亟待解决的关键问题。近年来，多项研究揭示了CD8+ T细胞的干性调控机制，发现了干细胞样CD8+ T细胞具有自我更新和增殖能力，阐明了该细胞亚群在维持持续性肿瘤免疫治疗应答中的重要性。本文论述了干细胞样CD8+ T 细胞的分子与功能特征、CD8+ T 细胞干性的细胞内外影响因素，归纳总结了目前靶向CD8+ T细胞的干性重编程策略，进一步展望了靶向CD8+ T细胞干性程序来提高肿瘤免疫疗法疗效的思路和方法。

CD8+ T cells are the major players in anti-tumor immune responses. Immune therapies have made significant breakthroughs in the field of cancer treatment by reshaping the ability of CD8+ T cells to kill tumor cells. But clinical benefits have been limited to some patients and certain cancer types. The key to improving cancer immunotherapy depends on how to overcome the CD8+ T cell dysfunctions. In recent years, quite a few researches have revealed the stemness regulation mechanisms of CD8+ T cells,discovered that stem-like CD8+ T cells possess self-renewal and proliferation abilities and stated the importance of this cell subgroup in maintaining sustained cancer immunotherapy responses. In this paper, we will review the molecular and functional characteristics of stem-cell like CD8+ T cells, and the intrinsic and extrinsic influencing factors of CD8+ T cell stemness, summarize the present stemness reprogramming strategies targeting CD8+ T cells, and further look into the ideas and methods of improving the therapeutic efficacy of cancer immunotherapy through targeting CD8+ T cells stemness programs.

国家自然科学基金（No. 81771682, No. 82071741）