CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8(+) T cells.
Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8(+) T cells.
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迄今为止，尚无任何免疫治疗方法能够完全克服T细胞耗竭，而T细胞耗竭仍是长期活化的效应细胞不可避免的命运，也是主要的治疗挑战。理解如何将CD8+TIL（肿瘤浸润淋巴细胞）从耗竭的效应状态重编程，仍然是一个难以实现的目标。我们的工作提供了证据，表明通过对T细胞进行正交基因工程改造，使其分泌一种结合IL-2Rβγ受体的IL-2变体以及警报素IL-33，可重编程过继转移的T细胞，使其获得一种新的合成效应状态，该状态偏离了经典的耗竭表型并展现出优越的效应功能。这些细胞成功克服了宿主中的稳态屏障，并在没有淋巴细胞清除或外源性细胞因子支持的情况下，实现了高水平的植入和肿瘤消退。我们的工作开启了一个新的机遇，即合理工程化改造合成CD8+T细胞状态，使其具备避免耗竭和控制晚期实体瘤的能力。
To date, no immunotherapy approaches have managed to fully overcome T-cell exhaustion, which remains a mandatory fate for chronically activated effector cells and a major therapeutic challenge. Understanding how to reprogram CD8 + tumor-infiltrating lymphocytes away from exhausted effector states remains an elusive goal.
Our work provides evidence that orthogonal gene engineering of T cells to secrete an interleukin (IL)-2 variant binding the IL-2Rβγ receptor and the alarmin IL-33 reprogrammed adoptively transferred T cells to acquire a novel, synthetic effector state, which deviated from canonical exhaustion and displayed superior effector functions. These cells successfully overcame homeostatic barriers in the host and led-in the absence of lymphodepletion or exogenous cytokine support-to high levels of engraftment and tumor regression.
Our work unlocks a new opportunity of rationally engineering synthetic CD8 + T-cell states endowed with the ability to avoid exhaustion and control advanced solid tumors.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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