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Literature Report

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

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
Cancer cell | 2023

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.

Pubmed ID: 37311414 RIS Download

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