Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune che...

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Bibliographic Details
Published in:Cancer cell Vol. 33; no. 4; p. 581
Main Authors: Zappasodi, Roberta, Merghoub, Taha, Wolchok, Jedd D
Format: Journal Article
Language:English
Published: United States 09.04.2018
Subjects:
Antibodies, Blocking - therapeutic use
B7-H1 Antigen - immunology
Clinical Trials as Topic
Combined Modality Therapy - methods
CTLA-4 Antigen - immunology
Humans
Immunotherapy - methods
Neoplasms - immunology
Neoplasms - therapy
Programmed Cell Death 1 Receptor - immunology
Tumor Burden - drug effects
tumor immunology
immunotherapy-based combinations
cancer immunotherapy
immune checkpoint blockade
ISSN:1878-3686, 1878-3686
Online Access:Get more information
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Summary:Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccell.2018.03.005