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The B7 Family and Cancer Therapy: Costimulation and Coinhibition

Authors' Affiliation: Howard Hughes Medical Institute, Immunology Program, Ludwig Center of Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: James P. Allison, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 415 East 68th Street, Box 470, New York, NY 10021. Phone: 646-888-2332; Fax: 646-422-0470; E-mail: allisonj{at}mskcc.org.

Abstract

The activation and development of an adaptive immune response is initiated by the engagement of a T-cell antigen receptor by an antigenic peptide-MHC complex. The outcome of this engagement is determined by both positive and negative signals, costimulation and coinhibition, generated mainly by the interaction between the B7 family and their receptor CD28 family. The importance of costimulation and coinhibition of T cells in controlling immune responses is exploited by tumors as immune evasion pathways. Absence of the expression of costimulatory B7 molecules renders tumors invisible to the immune system, whereas enhanced expression of inhibitory B7 molecules protects them from effective T cell destruction. Therefore, the manipulation of these pathways is crucial for developing effective tumor immunotherapy. Translation of our basic knowledge of costimulation and coinhibition into early clinical trials has shown considerable promise.

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