Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from "silent" to immunogenic.

Abstract

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.

• Authors: Michel Obeid, Theocharis Panaretakis, Antoine Tesniere, Nick Joza, Roberta Tufi, Lionel Apetoh, François Ghiringhelli, Laurence Zitvogel, Guido Kroemer
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 17 Pg. 7941-4 (Sep 01 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17804698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, Surface
• Calreticulin

Topics

• Animals
• Antigens, Surface (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects, immunology)
• Calreticulin (metabolism)
• Cell Death (drug effects)
• Humans
• Immune System (drug effects)
• Models, Biological