Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance

作者：Norma Bloy, Pauline Garcia, Céline M. Laumont, Jonathan M. Pitt, Antonella Sistigu, Gautier Stoll, Takahiro Yamazaki, Éric Bonneil, Aitziber Buqué, Juliette Humeau, Jan W. Drijfhout, Guillaume Meurice, Steffen Walter, Jens Fritsche, Toni Weinschenk, Hans‐Georg Rammensee, Cornelis J.M. Melief, Pierre Thibault, Claude Perreault, Jonathan Pol, Laurence Zitvogel, Laura Senovilla, Guido Kroemer · 发表于：Immunological Reviews · 年份：2017 · DOI：10.1111/imr.12582 · 被引用次数：102 · 研究领域：Immunotherapy and Immune Responses、Autophagy in Disease and Therapy、Endoplasmic Reticulum Stress and Disease

Summary Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the “eat‐me” signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells. Hence, both autophagy and polyploidization cause the emission of adjuvant signals that ultimately elicit immune control by CD8+ T lymphocytes. We investigated the possibility that autophagy and polyploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. Mass spectrometry led to the identification of peptides that were presented on major histocompatibility complex (MHC) class I molecules in an autophagy‐dependent fashion or that were specifically exposed on the surface of polyploid cells, yet lost upon passage of such cells through immunocompetent (but not immunodeficient) mice. However, the preferential recognition of autophagy‐competent and polyploid cells by the innate and cellular immune systems did not correlate with the preferential recognition of such peptides in vivo. Moreover, vaccination with such peptides was unable to elicit tumor growth‐inhi...