Coinhibitory Pathways in Immunotherapy for Cancer

The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity a...

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Bibliographic Details
Published in:Annual review of immunology 2016-05, Vol.34 (1), p.539-573
Main Authors: Baumeister, Susanne H, Freeman, Gordon J, Dranoff, Glenn, Sharpe, Arlene H
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
B7-H1 Antigen - immunology
cancer immunotherapy
CTLA-4
CTLA-4 Antigen - immunology
Humans
Immunotherapy - methods
Immunotherapy - trends
Lymphocyte Activation - drug effects
Neoplasms - immunology
Neoplasms - therapy
PD-1
PD-L1
Programmed Cell Death 1 Receptor - immunology
T-Lymphocytes - immunology
Tumor Escape
tumor immunity
Tumor Microenvironment
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Summary:The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer.
ISSN:0732-0582
1545-3278
DOI:10.1146/annurev-immunol-032414-112049