br Acknowledgments We apologize to the researchers who were

Acknowledgments We apologize to the researchers who were not referenced due to space limitations. We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health (R01CA160417 [D.T.], R01CA211070 [R.K.] and GM053396 [D.J.K.]), the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD [D.T.]), and the National Natural Science Foundation of China (81570154 [B.Z.]). GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE);and the SIRIC Cancer Research and Personalized Medicine (CARPEM).
Cell death plays many essential roles in development, senescence, tissue homeostasis, immunity, and stress tolerance in all multicellular organisms. While many environmental or developmental cues may trigger cell death, underlying molecular mechanisms are not always clear. Nevertheless, various forms of distinct cell death phenomena, such as apoptosis, programmed cell death (PCD), necrosis, and autophagy, have been described , , , . These cell death phenomena show mechanistically conserved as well as distinct features. For instance, the main morphological hallmarks of apoptosis in animal Azacyclonol are cell shrinkage, membrane blebbing, chromatin condensation, DNA laddering, and breakdown of the cell into apoptotic bodies that are subsequently removed . Although some of these features are shared by plant cell death pathways, apoptotic bodies are not formed during PCD in plant cells. Therefore, apoptosis appears to be mainly restricted to animals . Degradation of organelles and proteins and vacuolization are typically observed during autophagy . However, rather than being a distinct form of cell death, autophagy is either an executer or initiator of immunity-related and developmental cell death responses . Interestingly, while promoting PCD, autophagy antagonizes necrotic cell death in plants . Necrosis is mostly typified by cytoplasmic and organelle swelling, loss of membrane integrity, release of cellular proteins, and random DNA degradation . Although different cell death pathways might display certain commonalities, a distinguishing feature of a given cell death pathway is whether the cell death pathway is regulated by the host. In this respect, apoptosis in animals and PCD in plants differ from necrosis because the former is regulated by the host while the latter is not. This also implies that regulated cell death might be beneficial for the host. Indeed, autophagy, which is required for selective breakdown and recycling of certain cytoplasmic components during normal growth and development or stress adaptation, is considered a beneficial host response . Similarly, during apoptosis, cells commit suicide in an orderly fashion and this helps maintain normal cellular functions or protects the host from pathogens . For instance, hypersensitive response (HR), a term often used for controlled cell death occurring during an incompatible plant–pathogen interaction, protects the host from pathogen infection , . In contrast, during necrosis, host cells are degraded in an uncontrolled manner, leading to severe tissue damage and subsequent death of tissues, organs, and even the whole organism. Adding to the complexity, there is evidence suggesting that certain forms of necrosis, especially those induced by pathogens, might also be regulated by the host in both plants and animals , .