A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Ten years since the immune checkpoint inhibitor ipilimumab was approved for advanced melanoma, it is time to reflect on the lessons learned regarding modulation of the immune system to treat cancer and on novel approaches to further extend the efficacy of current and emerging immunotherapies. Here,...

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Bibliographic Details
Published in:Nature immunology Vol. 23; no. 5; pp. 660 - 670
Main Authors: Huang, Alexander C, Zappasodi, Roberta
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.05.2022
Subjects:
Immune checkpoint inhibitors
Immune system
Immunotherapy
Melanoma
Microenvironments
Monoclonal antibodies
Tumors
ISSN:1529-2908, 1529-2916, 1529-2916
Online Access:Get full text
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Summary:Ten years since the immune checkpoint inhibitor ipilimumab was approved for advanced melanoma, it is time to reflect on the lessons learned regarding modulation of the immune system to treat cancer and on novel approaches to further extend the efficacy of current and emerging immunotherapies. Here, we review the studies that led to our current understanding of the melanoma immune microenvironment in humans and the mechanistic work supporting these observations. We discuss how this information is guiding more precise analyses of the mechanisms of action of immune checkpoint blockade and novel immunotherapeutic approaches. Lastly, we review emerging evidence supporting the negative impact of melanoma metabolic adaptation on anti-tumor immunity and discuss how to counteract such mechanisms for more successful use of immunotherapy.
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ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/s41590-022-01141-1