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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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000967.full |
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| author | Chang Liu Creg J Workman Dario AA Vignali Christopher A Chuckran Tullia C Bruno |
| author_facet | Chang Liu Creg J Workman Dario AA Vignali Christopher A Chuckran Tullia C Bruno |
| author_sort | Chang Liu |
| collection | DOAJ |
| 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 (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 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. |
| format | Article |
| id | doaj-art-4c63cc756efa449daf9b583b14e83707 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-4c63cc756efa449daf9b583b14e837072025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000967Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapyChang Liu0Creg J Workman1Dario AA Vignali2Christopher A Chuckran3Tullia C Bruno44 Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USAAff1 grid.21925.3d0000000419369000University of Pittsburgh Pittsburgh PA USA1 Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA4 LUMICKS, Waltham, Massachusetts, USA1University of Pittsburgh, Pittsburgh, PA, USACheckpoint 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 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.https://jitc.bmj.com/content/8/2/e000967.full |
| spellingShingle | Chang Liu Creg J Workman Dario AA Vignali Christopher A Chuckran Tullia C Bruno Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy Journal for ImmunoTherapy of Cancer |
| 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 |
| url | https://jitc.bmj.com/content/8/2/e000967.full |
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