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PD-L1 checkpoint blockade promotes regulatory T cell activity that underlies therapy resistance by Mandy van Gulijk; Anneloes van Krimpen; Sjoerd Schetters; Mike Eterman; Marit van Elsas; Joanne Mankor; Larissa Klaase; Marjolein de Bruijn; Menno van Nimwegen; Tim van Tienhoven; Wilfred van Ijcken; Louis Boon; Johan van der Schoot; Martijn Verdoes; Ferenc Scheeren; Sjoerd H. van der Burg; Bart N. Lambrecht; Ralph Stadhouders; Floris Dammeijer; Joachim Aerts; Thorbald van Hall is a Immunology and Microbiology article available to read on EtoBox.

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Despite the clinical success of immune checkpoint blockade (ICB), in certain cancer types, most patients with cancer do not respond well. Furthermore, in patients for whom ICB is initially successful, this is often short-lived because of the development of resistance to ICB. The mechanisms underlying primary or secondary ICB resistance are incompletely understood. Here, we identified preferential activation and enhanced suppressive capacity of regulatory T cells (T reg cells) in αPD-L1 therapy–resistant solid tumor–bearing mice. T reg cell depletion reversed resistance to αPD-L1 with concomitant expansion of effector T cells. Moreover, we found that tumor-infiltrating T reg cells in human patients with skin cancer, and in patients with non–small cell lung cancer, up-regulated a suppressive transcriptional gene program after ICB treatment, which correlated with lack of treatment response. αPD-1/PD-L1–induced PD-1 + T reg cell activation was also seen in peripheral blood of patients with lung cancer and mesothelioma, especially in nonresponders. Together, these data reveal that treatment with αPD-1 and αPD-L1 unleashes the immunosuppressive role of T reg cells, resulting in therapy r

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Author

Mandy van Gulijk; Anneloes van Krimpen; Sjoerd Schetters; Mike Eterman; Marit van Elsas; Joanne Mankor; Larissa Klaase; Marjolein de Bruijn; Menno van Nimwegen; Tim van Tienhoven; Wilfred van Ijcken; Louis Boon; Johan van der Schoot; Martijn Verdoes; Ferenc Scheeren; Sjoerd H. van der Burg; Bart N. Lambrecht; Ralph Stadhouders; Floris Dammeijer; Joachim Aerts; Thorbald van Hall

Publisher

American Association for the Advancement of Science (AAAS)

Published

2023

Language

EN

Field

Immunology and Microbiology (Life Sciences)