干细胞样CD8^(+)T细胞:肿瘤免疫疗法的新生力量

Stem cell-like CD8^(+)T cells:a new pioneer in cancer immunotherapy

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.