Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model
Immune checkpoint blockade (ICB) therapies, such as anti-PD-1, have transformed cancer treatment, but many patients do not respond due to a non-inflammatory tumor microenvironment (TME). Here, we investigated the impact of targeting Atypical Chemokine Receptor 2 (ACKR2), which scavenges key chemokin...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494426 |
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| author | Muhammad Zaeem Noman Martyna Szpakowska Malina Xiao Ruize Gao Kris Van Moer Akinchan Kumar Markus Ollert Guy Berchem Andy Chevigné Bassam Janji |
| author_facet | Muhammad Zaeem Noman Martyna Szpakowska Malina Xiao Ruize Gao Kris Van Moer Akinchan Kumar Markus Ollert Guy Berchem Andy Chevigné Bassam Janji |
| author_sort | Muhammad Zaeem Noman |
| collection | DOAJ |
| description | Immune checkpoint blockade (ICB) therapies, such as anti-PD-1, have transformed cancer treatment, but many patients do not respond due to a non-inflammatory tumor microenvironment (TME). Here, we investigated the impact of targeting Atypical Chemokine Receptor 2 (ACKR2), which scavenges key chemokines involved in immune cell recruitment, on the improvement of anti-PD-1-based therapy. In a melanoma mouse model, we demonstrated that Ackr2 inhibition increases the release of proinflammatory chemokines CCL5 and CXCL10 and enhances the infiltration of NK cells, activated CD8+ and CD4+ effector T cells while reducing regulatory T cells (Tregs) in the TME. Targeting Ackr2 led to tumor growth inhibition, improved survival, and enhanced response to anti-PD-1 therapy. In BRAF- and NRAS-mutant melanoma patients, low ACKR2 expression or high CCL5/CXCL10 levels correlated with improved survival and higher CD8+ T cell markers. Targeting ACKR2 represents a promising approach for developing combination therapies, particularly for ‘cold’ ICB resistant tumors. |
| format | Article |
| id | doaj-art-677cfb5a060d44d29157e7822e8f44fe |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-677cfb5a060d44d29157e7822e8f44fe2025-08-20T03:18:11ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2494426Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse modelMuhammad Zaeem Noman0Martyna Szpakowska1Malina Xiao2Ruize Gao3Kris Van Moer4Akinchan Kumar5Markus Ollert6Guy Berchem7Andy Chevigné8Bassam Janji9Tumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgImmuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgImmuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgImmuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, LuxembourgTumor Immunotherapy and Microenvironment (TIME), Department of Cancer Research, Luxembourg Institute of Health (LIH), Luxembourg City, LuxembourgImmune checkpoint blockade (ICB) therapies, such as anti-PD-1, have transformed cancer treatment, but many patients do not respond due to a non-inflammatory tumor microenvironment (TME). Here, we investigated the impact of targeting Atypical Chemokine Receptor 2 (ACKR2), which scavenges key chemokines involved in immune cell recruitment, on the improvement of anti-PD-1-based therapy. In a melanoma mouse model, we demonstrated that Ackr2 inhibition increases the release of proinflammatory chemokines CCL5 and CXCL10 and enhances the infiltration of NK cells, activated CD8+ and CD4+ effector T cells while reducing regulatory T cells (Tregs) in the TME. Targeting Ackr2 led to tumor growth inhibition, improved survival, and enhanced response to anti-PD-1 therapy. In BRAF- and NRAS-mutant melanoma patients, low ACKR2 expression or high CCL5/CXCL10 levels correlated with improved survival and higher CD8+ T cell markers. Targeting ACKR2 represents a promising approach for developing combination therapies, particularly for ‘cold’ ICB resistant tumors.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494426Cancer immunotherapyACKR2immune checkpoint blockadeanti-PD-1melanomacombination immunotherapy |
| spellingShingle | Muhammad Zaeem Noman Martyna Szpakowska Malina Xiao Ruize Gao Kris Van Moer Akinchan Kumar Markus Ollert Guy Berchem Andy Chevigné Bassam Janji Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model OncoImmunology Cancer immunotherapy ACKR2 immune checkpoint blockade anti-PD-1 melanoma combination immunotherapy |
| title | Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model |
| title_full | Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model |
| title_fullStr | Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model |
| title_full_unstemmed | Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model |
| title_short | Targeting the atypical chemokine receptor 2 (Ackr2) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model |
| title_sort | targeting the atypical chemokine receptor 2 ackr2 improves the benefit of anti pd 1 immunotherapy in melanoma mouse model |
| topic | Cancer immunotherapy ACKR2 immune checkpoint blockade anti-PD-1 melanoma combination immunotherapy |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494426 |
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