Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity
Vennin, Claire; Cattaneo, Chiara M; Bosch, Leontien; Vegna, Serena; Ma, Xuhui; Damstra, Hugo G J; Martinovic, Moreno; Tsouri, Efi; Ilic, Mila; Azarang, Leyla; van Weering, Jan R T; Pulver, Emilia; Zeeman, Amber L; Schelfhorst, Tim; Lohuis, Jeroen O; Rios, Anne C; Dekkers, Johanna F; Akkari, Leila; Menezes, Renee; Medema, Rene; Baglio, Serena R; Akhmanova, Anna; Linn, Sabine C; Lemeer, Simone; Pegtel, Dirk M; Voest, Emile E; van Rheenen, Jacco
(2023) Cancer Cell, volume 41, issue 6, pp. 1170 - 1185.e12
(Article)
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
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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.
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Keywords: T cell therapy, T cells, extracellular vesicles, in vivo mode of action, taxanes, Oncology, Cancer Research
ISSN: 1535-6108
Publisher: Cell Press
Note: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
(Peer reviewed)