Taxanes trigger cancer cell killing in vivo by releasing cytotoxic extracellular vesicles

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. Researchers from the Netherlands Cancer Institute 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. The researchers 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. This 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.

Vennin C, Cattaneo CM, Bosch L, Vegna S, Ma X, Damstra HGJ, Martinovic M, Tsouri E, Ilic M, Azarang L, van Weering JRT, Pulver E, Zeeman AL, Schelfhorst T, Lohuis JO, Rios AC, Dekkers JF, Akkari L, Menezes R, Medema R, Baglio SR, Akhmanova A, Linn SC, Lemeer S, Pegtel DM, Voest EE, van Rheenen J. (2023) Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity. Cancer Cell 41(6):1170-1185.e12. [article]

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