Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model
Head and neck squamous cell carcinoma (HNSCC) continues to be among the most common malignancies worldwide with limited treatment options for patients. Targeting the PD-1/PDL-1 axis is currently the only FDA approved immune checkpoint inhibitor treatment for HNSCC. Novel therapies targeting other pa...
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| Format: | Article |
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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.2025.2477872 |
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| author | Felipe F. Lamenza Peyton Roth Puja Upadhaya Suvekshya Shrestha Sushmitha Jagadeesha Natalie Kazmierowicz Natalie Horn Hasan Pracha Sonali Dasari Steve Oghumu |
| author_facet | Felipe F. Lamenza Peyton Roth Puja Upadhaya Suvekshya Shrestha Sushmitha Jagadeesha Natalie Kazmierowicz Natalie Horn Hasan Pracha Sonali Dasari Steve Oghumu |
| author_sort | Felipe F. Lamenza |
| collection | DOAJ |
| description | Head and neck squamous cell carcinoma (HNSCC) continues to be among the most common malignancies worldwide with limited treatment options for patients. Targeting the PD-1/PDL-1 axis is currently the only FDA approved immune checkpoint inhibitor treatment for HNSCC. Novel therapies targeting other pathways are needed along with testing a combinational approach to find new and more efficient ways to treat this disease. We utilized a tamoxifen inducible TgfβR1/Pten deletion mouse model to explore the efficacy of combined anti-LAG-3 and anti-PD-1 therapy against tongue HNSCC and determine underlying immunological mechanisms. Combined anti-LAG-3/anti-PD-1 therapy was effective at decreasing the tumor burden and lymphatic metastasis compared to anti-LAG-3 treatment but not when compared to the anti-PD-1 treatment alone. Anti-tumoral effects of anti-PD1 and anti-LAG-3/anti-PD-1 combined therapy were associated with increased CD4+ and CD8+ T-cell proliferative responses in secondary lymphoid organs along with increased CD8+ T-cell tumor infiltration. Anti-LAG-3 treatment potentiated the anti-tumoral properties of CD4+ T-cells treated with anti-PD-1, including enhanced systemic IFN-γ production and TNF-α production in the tumor microenvironment. Further, anti-tumoral cytotoxic CD8+ T-cell effector function and granzyme B production were enhanced by anti-PD-1 and combinatorial anti-LAG-3/anti-PD-1 immunotherapy, resulting in greater tumor cell death. Our results demonstrate that anti-LAG-3 has the potential to enhance the efficacy of anti-PD-1 therapy; however, humanized mouse models that better recapitulate the human disease with FDA approved antibodies are needed to further characterize the efficacy of this treatment as a viable treatment option for HNSCC patients. |
| format | Article |
| id | doaj-art-9e237f6a13ae4a829ebd951aff930a74 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-9e237f6a13ae4a829ebd951aff930a742025-08-20T03:01:58ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2477872Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse modelFelipe F. Lamenza0Peyton Roth1Puja Upadhaya2Suvekshya Shrestha3Sushmitha Jagadeesha4Natalie Kazmierowicz5Natalie Horn6Hasan Pracha7Sonali Dasari8Steve Oghumu9Department of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USAHead and neck squamous cell carcinoma (HNSCC) continues to be among the most common malignancies worldwide with limited treatment options for patients. Targeting the PD-1/PDL-1 axis is currently the only FDA approved immune checkpoint inhibitor treatment for HNSCC. Novel therapies targeting other pathways are needed along with testing a combinational approach to find new and more efficient ways to treat this disease. We utilized a tamoxifen inducible TgfβR1/Pten deletion mouse model to explore the efficacy of combined anti-LAG-3 and anti-PD-1 therapy against tongue HNSCC and determine underlying immunological mechanisms. Combined anti-LAG-3/anti-PD-1 therapy was effective at decreasing the tumor burden and lymphatic metastasis compared to anti-LAG-3 treatment but not when compared to the anti-PD-1 treatment alone. Anti-tumoral effects of anti-PD1 and anti-LAG-3/anti-PD-1 combined therapy were associated with increased CD4+ and CD8+ T-cell proliferative responses in secondary lymphoid organs along with increased CD8+ T-cell tumor infiltration. Anti-LAG-3 treatment potentiated the anti-tumoral properties of CD4+ T-cells treated with anti-PD-1, including enhanced systemic IFN-γ production and TNF-α production in the tumor microenvironment. Further, anti-tumoral cytotoxic CD8+ T-cell effector function and granzyme B production were enhanced by anti-PD-1 and combinatorial anti-LAG-3/anti-PD-1 immunotherapy, resulting in greater tumor cell death. Our results demonstrate that anti-LAG-3 has the potential to enhance the efficacy of anti-PD-1 therapy; however, humanized mouse models that better recapitulate the human disease with FDA approved antibodies are needed to further characterize the efficacy of this treatment as a viable treatment option for HNSCC patients.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2477872LAG-3PD-1HNSCCT cell |
| spellingShingle | Felipe F. Lamenza Peyton Roth Puja Upadhaya Suvekshya Shrestha Sushmitha Jagadeesha Natalie Kazmierowicz Natalie Horn Hasan Pracha Sonali Dasari Steve Oghumu Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model OncoImmunology LAG-3 PD-1 HNSCC T cell |
| title | Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| title_full | Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| title_fullStr | Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| title_full_unstemmed | Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| title_short | Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| title_sort | efficacy of anti lag3 and anti pd 1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model |
| topic | LAG-3 PD-1 HNSCC T cell |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2477872 |
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