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

• Published in: Cell death & disease Vol. 9; no. 7; pp. 716 - 18
• Main Authors: Martins, Isabelle, Raza, Syed Qasim, Voisin, Laurent, Dakhli, Haithem, Allouch, Awatef, Law, Frédéric, Sabino, Dora, De Jong, Dorine, Thoreau, Maxime, Mintet, Elodie, Dugué, Delphine, Piacentini, Mauro, Gougeon, Marie-Lise, Jaulin, Fanny, Bertrand, Pascale, Brenner, Catherine, Ojcius, David M., Kroemer, Guido, Modjtahedi, Nazanine, Deutsch, Eric, Perfettini, Jean-Luc
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-06-2018; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/2; 13/31; 13/95; 14/19; 14/34; 14/63; 38/1; 82/80; Antibodies; Antitumor agents; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cancer; Cancer therapies; Cannibalism; Cell Biology; Cell Culture; Cell death; Cellular Biology; Chemotherapy; Cisplatin; Cytometry; Immunology; Ionizing radiation; Life Sciences; Medicin och hälsovetenskap; Oxaliplatin; p53 Protein; Paclitaxel; Radiation therapy; Transcription
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0747-y

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.