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

I. Martins, S.Q. Raza, L. Voisin, H. Dakhli, A. Allouch, F. Law, D. Sabino, D. De Jong, M. Thoreau, E. Mintet, D. Dugué, M. Piacentini, M.-L. Gougeon, F. Jaulin, P. Bertrand, C. Brenner, D.M. Ojcius, G. Kroemer, N. Modjtahedi, E. DeutschJ.-L. Perfettini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalCell Death and Disease
Issue number7
Publication statusPublished - 2018


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