Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

Wei, Spencer C.; Duffy, Colm R.; Allison, James P.

doi:10.1158/2159-8290.cd-18-0367

Cited by 3,088Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

Wei, Spencer C., Duffy, Colm R., Allison, James P.·2018·Cancer Discovery

DOI 10.1158/2159-8290.cd-18-0367

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Abstract

Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Insights into the underlying biological mechanisms and functions of these molecules have, however, lagged significantly behind. Such understanding will be essential for the rational design of next-generation immunotherapies. Here, we review the current state of our understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps in knowledge. Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069–86. ©2018 AACR.

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Authors: Wei, S. C., Duffy, C. R., & Allison, J. P.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Wei, Spencer C.
Allison, James P.
ORCID: Wei, Spencer C.
Duffy, Colm R.
Allison, James P.
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2018-09-01
Volume: 8
Issue: 9
Pages: 1069-1086
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-18-0367
OpenAlex: W2887577080
Semantic Scholar: d55fdb93cb09f363fee0cb685822f734afff73c8
Cited by: 3,088
References: 47
Citations by year: 2026: 236 · 2025: 345 · 2024: 376 · 2023: 420 · 2022: 473 · 2021: 513 · 2020: 451 · 2019: 252 · 2018: 18
FWCI: 32.29
Type: journal article
Language: en
Open access: closed
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
Funders: Parker Institute for Cancer Immunotherapy
University of Texas MD Anderson Cancer Center
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: immune checkpoint blockade, T cell costimulatory molecules, CTLA-4, PD-1, cancer immunotherapy, T cell activation
MeSH terms: Antineoplastic Agents, Immunological, Clinical Trials as Topic, Humans, Lymphocyte Activation, Neoplasms, T-Lymphocytes, CTLA-4 Antigen, Programmed Cell Death 1 Receptor

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Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

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