Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death

Isabelle Martins 1, 2 Syed Qasim Raza 1, 2, 3 Laurent Voisin 1, 2 Haithem Dakhli 1, 2 Awatef Allouch 1, 2 Frédéric Law 1, 2 Dora Sabino 4 Dorine de Jong 1, 2 Maxime Thoreau 1, 2 Elodie Mintet 1, 2 Delphine Dugué 1, 2 Mauro Piacentini 5, 6 Marie-Lise Gougeon 7 Fanny Jaulin 4 Pascale Bertrand 8 Catherine Brenner 9 David Ojcius 10 Guido Kroemer 11, 12, 13, 14 Nazanine Modjtahedi 1, 2 Eric Deutsch 1, 2 Jean-Luc Perfettini 1, 2
Abstract : Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.
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Isabelle Martins, Syed Qasim Raza, Laurent Voisin, Haithem Dakhli, Awatef Allouch, et al.. Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death. Cell Death and Disease , Nature Publishing Group, 2018, 9 (7), pp.716. ⟨10.1038/s41419-018-0747-y⟩. ⟨hal-02356534⟩

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