荷兰的安东尼·范·列文虎克医院Jacco van Rheenen团队近期取得重要工作进展，他们研究发现紫杉烷类可以通过诱导非经典T细胞毒性在体内触发癌细胞杀伤。相关研究成果2023年6月12日在线发表于《癌细胞》杂志上。

据介绍，虽然紫杉烷类药物的治疗并不总能带来临床益处，但所有患者都面临其有害副作用（如周围神经病变）的风险。了解紫杉烷的体内作用模式有助于设计改进的治疗方案。

研究人员证明在体内，紫杉烷直接触发T细胞以非规范、T细胞受体依赖的方式选择性杀伤癌症细胞。从机制上讲，紫杉烷诱导T细胞释放细胞毒性细胞外小泡，从而导致肿瘤细胞特异性凋亡，同时使健康的上皮细胞完好无损。研究人员利用这些发现开发了一种有效的治疗方法，该方法基于体外紫杉烷预处理T细胞的转移，从而避免了全身治疗的毒性。

总之，这一研究揭示了一种最常用的化学疗法的不同体内作用模式，并开辟了利用紫杉烷类T细胞依赖性抗肿瘤作用同时避免全身毒性的途径。

附：英文原文

Title: Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity

Author: Claire Vennin, Chiara M. Cattaneo, Leontien Bosch, Serena Vegna, Xuhui Ma, Hugo G.J. Damstra, Moreno Martinovic, Efi Tsouri, Mila Ilic, Leyla Azarang, Jan R.T. van Weering, Emilia Pulver, Amber L. Zeeman, Tim Schelfhorst, Jeroen O. Lohuis, Anne C. Rios, Johanna F. Dekkers, Leila Akkari, Renee Menezes, Rene Medema, Serena R. Baglio, Anna Akhmanova, Sabine C. Linn, Simone Lemeer, Dirk M. Pegtel, Emile E. Voest, Jacco van Rheenen

Issue&Volume: 2023/06/12

Abstract: Although treatment with taxanes does not always lead to clinical benefit, all patients are at risk of their detrimental side effects such as peripheral neuropathy. Understanding the in vivo mode of action of taxanes can help design improved treatment regimens. Here, we demonstrate that in vivo, taxanes directly trigger T cells to selectively kill cancer cells in a non-canonical, T cell receptor-independent manner. Mechanistically, taxanes induce T cells to release cytotoxic extracellular vesicles, which lead to apoptosis specifically in tumor cells while leaving healthy epithelial cells intact. We exploit these findings to develop an effective therapeutic approach, based on transfer of T cells pre-treated with taxanes ex vivo, thereby avoiding toxicity of systemic treatment. Our study reveals a different in vivo mode of action of one of the most commonly used chemotherapies, and opens avenues to harness T cell-dependent anti-tumor effects of taxanes while avoiding systemic toxicity.

DOI: 10.1016/j.ccell.2023.05.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00176-9