TY - JOUR
T1 - Immunogenic cancer cell death
T2 - a key-lock paradigm
AU - Tesniere, Antoine
AU - Apetoh, Lionel
AU - Ghiringhelli, Francois
AU - Joza, Nicholas
AU - Panaretakis, Theocharis
AU - Kepp, Oliver
AU - Schlemmer, Frederic
AU - Zitvogel, Laurence
AU - Kroemer, Guido
N1 - Funding Information:
The authors are supported by grants from the Ligue Nationale contre le Cancer, the European Union, Cancéropôle Ile-de-France, Institut National du Cancer, and Association for International Cancer Research. AT is supported by INSERM, LA receives grants from Fondation pour la recherche médicale, TP is supported by a grant from the Swedish Research Council, OK receives fellowship from EMBO and GK is supported by Agence Nationale pour la Recherche. The authors declare no competing financial interests.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - Physiological cell death, which occurs as a continuous byproduct of cellular turnover, is non-immunogenic or even tolerogenic, thereby avoiding autoimmunity. By contrast, cancer cell death elicited by radiotherapy and some chemotherapeutic agents such as anthracyclines is immunogenic. Recent data suggest that innate and cognate immune responses elicited by such anti-cancer agents are required for an optimal therapeutic outcome, underscoring the clinical relevance of immunogenic cell death. Here we discuss the concept that immunogenic death involves changes in the composition of the cell surface, as well as the release of soluble immunogenic signals that occur in a defined temporal sequence. This 'key' then operates on a series of receptors expressed by dendritic cells (DC, the 'lock') to allow for the presentation of tumor antigens to T cells and for the initiation of a productive immune response. Immunogenic cell death is characterized by the early cell surface exposure of chaperones including calreticulin and/or heat shock proteins, which determine the uptake of tumor antigens and/or affect DC maturation. Moreover, the late release of High mobility group box 1 (HMGB1), which acts on toll-like receptor 4 (TLR4), is required for optimal presentation of antigens from dying tumor cells. Nonetheless, numerous details on the molecular events that define immunogenicity remain to be defined, both at the level of the dying cancer cells and at the level of the responding innate effectors.
AB - Physiological cell death, which occurs as a continuous byproduct of cellular turnover, is non-immunogenic or even tolerogenic, thereby avoiding autoimmunity. By contrast, cancer cell death elicited by radiotherapy and some chemotherapeutic agents such as anthracyclines is immunogenic. Recent data suggest that innate and cognate immune responses elicited by such anti-cancer agents are required for an optimal therapeutic outcome, underscoring the clinical relevance of immunogenic cell death. Here we discuss the concept that immunogenic death involves changes in the composition of the cell surface, as well as the release of soluble immunogenic signals that occur in a defined temporal sequence. This 'key' then operates on a series of receptors expressed by dendritic cells (DC, the 'lock') to allow for the presentation of tumor antigens to T cells and for the initiation of a productive immune response. Immunogenic cell death is characterized by the early cell surface exposure of chaperones including calreticulin and/or heat shock proteins, which determine the uptake of tumor antigens and/or affect DC maturation. Moreover, the late release of High mobility group box 1 (HMGB1), which acts on toll-like receptor 4 (TLR4), is required for optimal presentation of antigens from dying tumor cells. Nonetheless, numerous details on the molecular events that define immunogenicity remain to be defined, both at the level of the dying cancer cells and at the level of the responding innate effectors.
UR - http://www.scopus.com/inward/record.url?scp=50549102898&partnerID=8YFLogxK
U2 - 10.1016/j.coi.2008.05.007
DO - 10.1016/j.coi.2008.05.007
M3 - Review article
C2 - 18573340
AN - SCOPUS:50549102898
SN - 0952-7915
VL - 20
SP - 504
EP - 511
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
IS - 5
ER -