[Antitumoral immunization during cancer chemotherapy]

Bull Acad Natl Med. 2012 Jun;196(6):1075-86.
[Article in French]

Abstract

Most anticancer agents are thought to act through direct induction of tumoral, stromal and endothelial cell death by apoptosis or necrosis. In a 2008 issue of Bulletin de l'Académie Nationale de Médecine, we described an alternative (or complementary) theory whereby the immune system participates in the antitumoral effects of some chemotherapy or radiotherapy regimens by promoting an immunogenic cell death pathway. In particular, we showed the critical importance of two pre-mortem stressors that determine the immunogenicity of dying tumor cells. The first, an ER stress response culminating in calreticuline exposure at the tumor cell surface, is mandatory for the uptake and efficient phagocytosis of apoptotic bodies by dendritic cells. In the second, autophagy leads to the release of ATP by dying tumor cells, resulting in the recruitment of inflammatory phagocytes and antigen-presenting cells, and also triggering the inflammasome that causes IL-1beta release and CD8+ T cell polarization. The tumor microenvironment changes following chemotherapy, favoring sequential accumulation of a series of innate and cognate effectors that act in a coordinated fashion to promote tumor eradication. These findings will help to identify immune predictors of the response to conventional anticancer treatments and to design innovative combinatorial immunochemotherapy regimens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigen Presentation / drug effects*
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / immunology
  • Autophagy / drug effects*
  • Autophagy / immunology
  • Calreticulin / metabolism
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Endoplasmic Reticulum Stress
  • HMGB1 Protein / physiology
  • Humans
  • Inflammasomes / immunology
  • Interleukin-1beta / metabolism
  • Lymphocyte Activation / drug effects*
  • Mice
  • Models, Immunological*
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Protein Transport
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Toll-Like Receptor 4 / immunology

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Calreticulin
  • Cytokines
  • HMGB1 Protein
  • Inflammasomes
  • Interleukin-1beta
  • Toll-Like Receptor 4
  • Adenosine Triphosphate