Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity.
By destroying tumor cells, conventional anticancer therapies may stimulate the host immune system to eliminate residual disease. Anthracyclines, oxaliplatin, and ionizing irradiation activate a type of tumor cell death that elicits efficient anticancer immune responses depending on interferon gamma (IFNgamma) and the IFNgamma receptor. Thus, dying tumor cells emit danger signals that are perceived by dendritic cells (DC), which link innate and cognate immune responses. Recently, we observed that ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. These results imply a novel danger signal, ATP, and a novel receptor, P2RX7, in the chemotherapy-elicited anticancer immune response.
Aymeric
Laetitia
L
U805 and CIC BT507 INSERM, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805 Villejuif, France. zitvogel@igr.fr
Apetoh
Lionel
L
Ghiringhelli
François
F
Tesniere
Antoine
A
Martins
Isabelle
I
Kroemer
Guido
G
Smyth
Mark J
MJ
Zitvogel
Laurence
L
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D016923:Cell Death / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000096743:Interferon gamma Receptor
D000255:Adenosine Triphosphate; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor