Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells
Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most diagnosed malignancies globally, with a 5-year survival rate of only 40–50%. Current therapies are limited to aggressive chemoradiotherapy combinations and disfiguring resection. Recent research has demonstrated that inhibitio...
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Springer
2025-05-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04081-5 |
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| author | Anna R. Bopp Felipe F. Lamenza Puja Upadhaya Nathan M. Ryan Natalie Kazmierowicz Pete P. Jordanides Arham Siddiqui Sherefuddin H. Pracha Peyton Roth O. Hans Iwenofu Steve Oghumu |
| author_facet | Anna R. Bopp Felipe F. Lamenza Puja Upadhaya Nathan M. Ryan Natalie Kazmierowicz Pete P. Jordanides Arham Siddiqui Sherefuddin H. Pracha Peyton Roth O. Hans Iwenofu Steve Oghumu |
| author_sort | Anna R. Bopp |
| collection | DOAJ |
| description | Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most diagnosed malignancies globally, with a 5-year survival rate of only 40–50%. Current therapies are limited to aggressive chemoradiotherapy combinations and disfiguring resection. Recent research has demonstrated that inhibition of Bruton’s tyrosine kinase (BTK) by ibrutinib is an effective treatment for aggressive solid cancers. However, little is known about the effects of ibrutinib on aggressive HNSCC. We tested the efficacy of ibrutinib against HNSCC in vitro and in a metastatic, aggressive MOC2 orthotopic murine model and determined the underlying mechanisms. Ibrutinib decreased cancer cell growth in vitro, reduced tumor burden in vivo, decreased metastasis to the tumor draining lymph nodes and lungs, and enhanced overall survival outcomes. Flow cytometric analysis revealed decreased infiltration of tumor-infiltrating immunosuppressive T cells expressing the co-inhibitory markers PD-1, LAG-3, and IL-10. Furthermore, ibrutinib treatment increased cytotoxic T cell infiltration into the tumor microenvironment. Further analysis demonstrated that the effects on immunosuppressive T cell phenotypes were directly mediated by ibrutinib. Immunosuppressive myeloid cells were also observed to express lower levels of PDL1 in ibrutinib-treated mice. Our study demonstrates the potential of BTK inhibitors, specifically ibrutinib, in the treatment of HNSCC, mediated by its inhibitory effect on HNSCC cancer cell growth and metastasis, as well as modulation of the T cell anti-tumor immune microenvironment. |
| format | Article |
| id | doaj-art-0e6a482d7bff452c8cc6fc77173e1d16 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-0e6a482d7bff452c8cc6fc77173e1d162025-08-20T03:45:10ZengSpringerCancer Immunology, Immunotherapy1432-08512025-05-0174711710.1007/s00262-025-04081-5Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cellsAnna R. Bopp0Felipe F. Lamenza1Puja Upadhaya2Nathan M. Ryan3Natalie Kazmierowicz4Pete P. Jordanides5Arham Siddiqui6Sherefuddin H. Pracha7Peyton Roth8O. Hans Iwenofu9Steve Oghumu10Department of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical CenterAbstract Head and neck squamous cell carcinoma (HNSCC) is one of the most diagnosed malignancies globally, with a 5-year survival rate of only 40–50%. Current therapies are limited to aggressive chemoradiotherapy combinations and disfiguring resection. Recent research has demonstrated that inhibition of Bruton’s tyrosine kinase (BTK) by ibrutinib is an effective treatment for aggressive solid cancers. However, little is known about the effects of ibrutinib on aggressive HNSCC. We tested the efficacy of ibrutinib against HNSCC in vitro and in a metastatic, aggressive MOC2 orthotopic murine model and determined the underlying mechanisms. Ibrutinib decreased cancer cell growth in vitro, reduced tumor burden in vivo, decreased metastasis to the tumor draining lymph nodes and lungs, and enhanced overall survival outcomes. Flow cytometric analysis revealed decreased infiltration of tumor-infiltrating immunosuppressive T cells expressing the co-inhibitory markers PD-1, LAG-3, and IL-10. Furthermore, ibrutinib treatment increased cytotoxic T cell infiltration into the tumor microenvironment. Further analysis demonstrated that the effects on immunosuppressive T cell phenotypes were directly mediated by ibrutinib. Immunosuppressive myeloid cells were also observed to express lower levels of PDL1 in ibrutinib-treated mice. Our study demonstrates the potential of BTK inhibitors, specifically ibrutinib, in the treatment of HNSCC, mediated by its inhibitory effect on HNSCC cancer cell growth and metastasis, as well as modulation of the T cell anti-tumor immune microenvironment.https://doi.org/10.1007/s00262-025-04081-5HNSCCIbrutinibT cellsInterleukin 10 |
| spellingShingle | Anna R. Bopp Felipe F. Lamenza Puja Upadhaya Nathan M. Ryan Natalie Kazmierowicz Pete P. Jordanides Arham Siddiqui Sherefuddin H. Pracha Peyton Roth O. Hans Iwenofu Steve Oghumu Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells Cancer Immunology, Immunotherapy HNSCC Ibrutinib T cells Interleukin 10 |
| title | Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells |
| title_full | Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells |
| title_fullStr | Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells |
| title_full_unstemmed | Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells |
| title_short | Inhibition of head and neck squamous cell carcinoma by Bruton’s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells |
| title_sort | inhibition of head and neck squamous cell carcinoma by bruton s tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive t cells |
| topic | HNSCC Ibrutinib T cells Interleukin 10 |
| url | https://doi.org/10.1007/s00262-025-04081-5 |
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