@article{ca0ff15740744564b26aecbd867d0b25,
title = "Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity",
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.",
keywords = "T cell therapy, T cells, extracellular vesicles, in vivo mode of action, taxanes",
author = "Claire Vennin and Cattaneo, {Chiara M.} and Leontien Bosch and Serena Vegna and Xuhui Ma and Damstra, {Hugo G.J.} and Moreno Martinovic and Efi Tsouri and Mila Ilic and Leyla Azarang and {van Weering}, {Jan R.T.} and Emilia Pulver and Zeeman, {Amber L.} and Tim Schelfhorst and Lohuis, {Jeroen O.} and Rios, {Anne C.} and Dekkers, {Johanna F.} and Leila Akkari and Renee Menezes and Rene Medema and Baglio, {Serena R.} and Anna Akhmanova and Linn, {Sabine C.} and Simone Lemeer and Pegtel, {Dirk M.} and Voest, {Emile E.} and {van Rheenen}, Jacco",
note = "Funding Information: Funding: This work was supported by the Netherlands Organization of Scientific Research NWO (Vici grant 09150182110004 , CancerGenomics.nl , and the Josef Steiner Cancer Research Foundation (JvR). CV is funded by a fellowship from the Human Frontiers in Science Program . The funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the paper; or in the decision to submit the paper for publication. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = jun,
day = "12",
doi = "https://doi.org/10.1016/j.ccell.2023.05.009",
language = "English",
volume = "41",
pages = "1170--1185.e12",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}