Journal Article Epublish
PubMed: 40445239 DOI: 10.1007/s00262-025-04081-5
Inhibition of head and neck squamous cell carcinoma by Bruton's tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells.
Cancer Immunol Immunother 74(7):227
Authors: 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
Affiliations
- Department of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 249 Evans Hall, 520 King Ave. Columbus, OH, 43201, USA.
- Department of Pathology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 249 Evans Hall, 520 King Ave. Columbus, OH, 43201, USA.
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.
MeSH
Cells, Growth, Carcinoma, Squamous Cell, Neoplasms, Immunotherapy, Squamous Cell Carcinoma Of Head And Neck, Neoplasm Metastasis, Protein-Tyrosine Kinases, Agammaglobulinaemia Tyrosine Kinase, Tyrosine, Therapeutics