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Trends Immunol. 2018 Aug;39(8):624-631. doi: 10.1016/j.it.2018.05.001. Epub 2018 May 22.

Defining and Understanding Adaptive Resistance in Cancer Immunotherapy.

Author information

1
Section of Hematology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
2
Section of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
3
Section of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: lieping.chen@yale.edu.

Abstract

Despite the unprecedented tumor regression and long-term survival benefit observed with anti-programmed death (PD) [anti-PD-1 or anti-B7-homolog 1 (B7-H1)] therapy in patients with advanced cancers, a large portion of patients do not benefit from such treatment and a fraction of responders relapse. Current efforts to overcome resistance and improve efficacy of anti-PD therapy require a clear understanding of resistance and should precede current avenues using random combinations with available treatment regimens. Here, we categorized three types of resistance, namely target-missing, primary, and acquired resistance. This categorization requires reliable, accurate tissue sampling and appropriate interpretation of results based on the four classifications of tumor immunity in the microenvironment (TIME). We believe that fundamental understanding of these complex tumor-immune interactions and of the cellular and molecular mechanisms underlying these types of true resistance is the key for targeting the right targets in combination with or beyond anti-PD therapy in the future.

KEYWORDS:

B7-H1; PD-1; cancer; immunotherapy; resistance

PMID:
29802087
PMCID:
PMC6066429
DOI:
10.1016/j.it.2018.05.001
[Indexed for MEDLINE]
Free PMC Article

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