Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy.

Journal for Immunotherapy of Cancer
Christopher A ChuckranDario Aa Vignali

Abstract

Checkpoint blockade immunotherapy established a new paradigm in cancer treatment: for certain patients curative treatment requires immune reinvigoration. Despite this monumental advance, only 20%-30% of patients achieve an objective response to standard of care immunotherapy, necessitating the consideration of alternative targets. Optimal strategies will not only stimulate CD8+ T cells, but concomitantly modulate immunosuppressive cells in the tumor microenvironment (TME), most notably regulatory T cells (Treg cells). In this context, the immunoregulatory receptor Neuropilin-1 (NRP1) is garnering renewed attention as it reinforces intratumoral Treg cell function amidst inflammation in the TME. Loss of NRP1 on Treg cells in mouse models restores antitumor immunity without sacrificing peripheral tolerance. Enrichment of NRP1+ Treg cells is observed in patients across multiple malignancies with cancer, both intratumorally and in peripheral sites. Thus, targeting NRP1 may safely undermine intratumoral Treg cell fitness, permitting enhanced inflammatory responses with existing immunotherapies. Furthermore, NRP1 has been recently found to modulate tumor-specific CD8+ T cell responses. Emerging data suggest that NRP1 restricts CD8+ T ...Continue Reading

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Citations

Nov 13, 2020·Chinese Medical Journal·Shao-Dan LiuYong-Xiang Zhao
Mar 19, 2021·Frontiers in Oncology·Anjali Rohatgi, John M Kirkwood
Apr 1, 2021·ACS Chemical Neuroscience·Samantha Perez-MillerRajesh Khanna
Jul 13, 2021·Frontiers in Cellular Neuroscience·Adonis SferaZisis Kozlakidis
Jun 29, 2021·Frontiers in Immunology·Ellen N ScottDario A A Vignali

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Methods Mentioned

BETA
immunoprecipitation
transgenic
xenograft

Clinical Trials Mentioned

NCT03565445

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