Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death

Abhishek D. Garg, Lorenzo Galluzzi, Lionel Apetoh, Thais Baert, Raymond B. Birge, José Manuel Bravo-San Pedro, Karine Breckpot, David Brough, Ricardo Chaurio, Mara Cirone, An Coosemans, Pierre G. Coulie, Dirk De Ruysscher, Luciana Dini, Peter de Witte, Aleksandra M. Dudek-Peric, Alberto Faggioni, Jitka Fucikova, Udo S. Gaipl, Jakub Golab, Marie-Lise Gougeon, Michael R. Hamblin, Akseli Hemminki, Martin Herrmann, James W. Hodge, Oliver Kepp, Guido Kroemer, Dmitri V. Krysko, Walter G. Land, Frank Madeo, Angelo A. Manfredi, Stephen R. Mattarollo, Christian Maueroder, Nicolò Merendino, Gabriele Multhoff, Thomas Pabst, Jean-Ehrland Ricci, Chiara Riganti, Erminia Romano, Nicole Rufo, Mark J. Smyth, Jürgen Sonnemann, Radek Spisek, John Stagg, Erika Vacchelli, Peter Vandenabeele, Lien Vandenberk, Benoit J. Van den Eynde, Stefaan Van Gool, Francesca Velotti, Laurence Zitvogel, Patrizia Agostinis

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.