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

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 consi...

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Autores principales: Chuckran, Christopher A, Liu, Chang, Bruno, Tullia C, Workman, Creg J, Vignali, Dario AA
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368550/
https://www.ncbi.nlm.nih.gov/pubmed/32675311
http://dx.doi.org/10.1136/jitc-2020-000967
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author Chuckran, Christopher A
Liu, Chang
Bruno, Tullia C
Workman, Creg J
Vignali, Dario AA
author_facet Chuckran, Christopher A
Liu, Chang
Bruno, Tullia C
Workman, Creg J
Vignali, Dario AA
author_sort Chuckran, Christopher A
collection PubMed
description 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 (T(reg) cells). In this context, the immunoregulatory receptor Neuropilin-1 (NRP1) is garnering renewed attention as it reinforces intratumoral T(reg) cell function amidst inflammation in the TME. Loss of NRP1 on T(reg) cells in mouse models restores antitumor immunity without sacrificing peripheral tolerance. Enrichment of NRP1(+) T(reg) cells is observed in patients across multiple malignancies with cancer, both intratumorally and in peripheral sites. Thus, targeting NRP1 may safely undermine intratumoral T(reg) 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 cell reinvigoration in response to checkpoint inhibitors, and more importantly, acts as a barrier to the long-term durability of CD8(+) T cell-mediated tumor immunosurveillance. These novel and distinct regulatory mechanisms present an exciting therapeutic opportunity. This review will discuss the growing literature on NRP1-mediated immune modulation which provides a strong rationale for categorizing NRP1 as both a key checkpoint in the TME as well as an immunotherapeutic target with promise either alone or in combination with current standard of care therapeutic regimens.
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spelling pubmed-73685502020-07-22 Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy Chuckran, Christopher A Liu, Chang Bruno, Tullia C Workman, Creg J Vignali, Dario AA J Immunother Cancer Review 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 (T(reg) cells). In this context, the immunoregulatory receptor Neuropilin-1 (NRP1) is garnering renewed attention as it reinforces intratumoral T(reg) cell function amidst inflammation in the TME. Loss of NRP1 on T(reg) cells in mouse models restores antitumor immunity without sacrificing peripheral tolerance. Enrichment of NRP1(+) T(reg) cells is observed in patients across multiple malignancies with cancer, both intratumorally and in peripheral sites. Thus, targeting NRP1 may safely undermine intratumoral T(reg) 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 cell reinvigoration in response to checkpoint inhibitors, and more importantly, acts as a barrier to the long-term durability of CD8(+) T cell-mediated tumor immunosurveillance. These novel and distinct regulatory mechanisms present an exciting therapeutic opportunity. This review will discuss the growing literature on NRP1-mediated immune modulation which provides a strong rationale for categorizing NRP1 as both a key checkpoint in the TME as well as an immunotherapeutic target with promise either alone or in combination with current standard of care therapeutic regimens. BMJ Publishing Group 2020-07-15 /pmc/articles/PMC7368550/ /pubmed/32675311 http://dx.doi.org/10.1136/jitc-2020-000967 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Review
Chuckran, Christopher A
Liu, Chang
Bruno, Tullia C
Workman, Creg J
Vignali, Dario AA
Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title_full Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title_fullStr Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title_full_unstemmed Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title_short Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
title_sort neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368550/
https://www.ncbi.nlm.nih.gov/pubmed/32675311
http://dx.doi.org/10.1136/jitc-2020-000967
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