Sex Differences in Murine Models of Head and Neck Squamous Cell Carcinoma
Sabrina Siegan, Carly Amato-Menker, Quinn Hopen
Jennifer Franko
Like many cancers, sex differences in the incidence and mortality rates of HNSCC have been identified. In West Virginia, the annual average-age adjusted incidence rate for oral/pharyngeal cancers is 20.1%:7% (male-to-female). Mortality rates trend similarly. Potent anti-tumor immune responses play an important role in inhibiting HNSCC. Consequently, immunotherapies that enhance anti-tumor immunity are being utilized to improve outcomes. Interestingly, sex disparities in immunotherapeutic efficacies have been identified, suggesting anti-tumor immunity may be differentially regulated in males vs. females. The goal of the current study was to determine if murine HNSCC models mimic the sexual dimorphic nature of human disease and provide suitable models for future studies investigating sex-specific anti-tumor immunity. Model 1: Male and female four-core genotype mice were orthotopically injected (tongue) with a syngeneic murine oral squamous cell carcinoma cell line. Model 2: HNSCC was spontaneously induced by exposing animals to the chemical carcinogen 4-nitroquinoline-N-oxide (4-NQO). Tumor size and incidence were evaluated weekly for 6 (Model 1) or 16 (Model 2) weeks. Similar to human disease, larger tumors with earlier onset, were noted in male mice in both models. Using these models, future studies will evaluate the influence of sex-specific immunity on HNSCC susceptibility, disease progression and immunotherapeutic efficacy.
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