Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype
Abstract Tumor‐associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9Hi TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-04-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202309026 |
| _version_ | 1797202477895909376 |
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| author | Noah Enbergs Elias A. Halabi Anne‐Gaëlle Goubet Kelton Schleyer Ina R. Fredrich Rainer H. Kohler Christopher S. Garris Mikaël J. Pittet Ralph Weissleder |
| author_facet | Noah Enbergs Elias A. Halabi Anne‐Gaëlle Goubet Kelton Schleyer Ina R. Fredrich Rainer H. Kohler Christopher S. Garris Mikaël J. Pittet Ralph Weissleder |
| author_sort | Noah Enbergs |
| collection | DOAJ |
| description | Abstract Tumor‐associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9Hi TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM‐specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small‐molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM‐avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM‐specific states, an insight a novel therapeutic anticancer approach is used to discover. |
| first_indexed | 2024-04-24T08:04:04Z |
| format | Article |
| id | doaj.art-9ae6b327a4c14e03ba83a5d83d68b25c |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T08:04:04Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-9ae6b327a4c14e03ba83a5d83d68b25c2024-04-17T12:48:22ZengWileyAdvanced Science2198-38442024-04-011115n/an/a10.1002/advs.202309026Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor PhenotypeNoah Enbergs0Elias A. Halabi1Anne‐Gaëlle Goubet2Kelton Schleyer3Ina R. Fredrich4Rainer H. Kohler5Christopher S. Garris6Mikaël J. Pittet7Ralph Weissleder8Center for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USADepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandCenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USACenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USADepartment of Pathology and Immunology University of Geneva Geneva 1211 SwitzerlandCenter for Systems Biology Massachusetts General Hospital 185 Cambridge St, CPZN 5206 Boston MA 02114 USAAbstract Tumor‐associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9Hi TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM‐specific therapeutics to exploit this new biological understanding. Here, the discovery and characterization of multiple small‐molecule enhancers of chemokine ligand 9 (CXCL9) and their targeted delivery in a TAM‐avid systemic nanoformulation is reported. With this strategy, it is efficient encapsulation and release of multiple drug loads that can efficiently induce CXCL9 expression in macrophages, both in vitro and in vivo in a mouse tumor model. These observations provide a window into the molecular features that define TAM‐specific states, an insight a novel therapeutic anticancer approach is used to discover.https://doi.org/10.1002/advs.202309026CXCL9IFNgmacrophagenanoparticlesPARP7polarization |
| spellingShingle | Noah Enbergs Elias A. Halabi Anne‐Gaëlle Goubet Kelton Schleyer Ina R. Fredrich Rainer H. Kohler Christopher S. Garris Mikaël J. Pittet Ralph Weissleder Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype Advanced Science CXCL9 IFNg macrophage nanoparticles PARP7 polarization |
| title | Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype |
| title_full | Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype |
| title_fullStr | Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype |
| title_full_unstemmed | Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype |
| title_short | Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype |
| title_sort | pharmacological polarization of tumor associated macrophages toward a cxcl9 antitumor phenotype |
| topic | CXCL9 IFNg macrophage nanoparticles PARP7 polarization |
| url | https://doi.org/10.1002/advs.202309026 |
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