Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from "silent" to immunogenic.
In contrast to prior belief, tumor cell apoptosis is not necessarily silent but can be immunogenic. By tracing how anthracyclines and gamma-irradiation trigger immunogenic cell deaths, we found that they were causally connected to the exposure of calreticulin on the tumor cell surface, before apoptosis in the tumor cell itself occurred. Furthermore, we showed that calreticulin exposure was necessary and sufficient to increase proimmunogenic killing by other chemotherapies. Our findings suggest that calreticulin could serve as a biomarker to predict therapy-associated immune responses, and that tactics to expose calreticulin might improve the clinical efficacy of many cancer therapies.
Obeid
Michel
M
INSERM, U848, F-94805, Villejuif, France.
Panaretakis
Theocharis
T
Tesniere
Antoine
A
Joza
Nick
N
Tufi
Roberta
R
Apetoh
Lionel
L
Ghiringhelli
François
F
Zitvogel
Laurence
L
Kroemer
Guido
G
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D037282:Calreticulin / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008954:Models, Biological