Cancers of the oral cavity and pharynx remain among the 10 most prevalent cancers in the United States. Signal Transducer and Activation of Transcription 1 (STAT1) is a transcription factor primarily involved in mediating responses to IFNs, as well as interleukin (IL) 21, 27, and 35. STAT1 has been shown to promote or suppress tumors in different cancer types, but its role in oral cavity cancers has not been examined. We examined the role of STAT1 in oral cancer using orthotopic models in wild-type (WT) and STAT1-deficient BALB/c mice. Metastatic (LY2) or nonmetastatic (B4B8) HNSCC cell lines were injected into the oral cavity and tumor development was monitored over a period of three or six weeks, respectively. At terminal sacrifice, tumors, spleens, draining lymph nodes, and bone marrow tissues were analyzed for tumor growth, metastasis, and immunologic responses. Tumors from STAT1-deficient mice injected with B4B8 cells were twice as large as tumors from WT mice. Interestingly, LY2-injected STAT1-deficient mice possessed tumors that were five times as large as tumors from LY2-injected WT mice. The increased tumor burdens in metastatic tumors were associated with a decrease in CD4+ and CD8+ T-cell infiltration into the draining lymph nodes of tumor-bearing STAT1-deficient mice compared to WT mice. Further, lymph node and splenic CD4+ and CD8+ T cells in tumor-bearing STAT1-deficient mice produced significantly lower TNF-alpha compared to WT mice. Finally, tumor-bearing STAT1-deficient mice displayed a significant accumulation of CD11b+ Ly6G+ myeloid cells in the spleens and bone marrow compared to WT counterparts in both metastatic and nonmetastatic HNSCC models. Our results demonstrate that STAT1 mediates resistance to oral tumor development that is associated with enhanced T-cell migration, TNF-alpha mediated antitumor T-cell responses, and diminished accumulation of tumor-promoting CD11b+ Ly6G+ myeloid cells.
Citation Format: Nathan Ryan, Kelvin Anderson, Greta Volpedo, Omar Hamza, Sanjay Varikuti, Abhay Satoskar, Steve Oghumu. STAT1 mediates resistance to experimental oral cancer that is associated with enhanced antitumor T-cell responses [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A11.