Giovana Thomas, M.D.
- Associate Professor
Head and neck surgery, research in immunology of head and neck cancer. Head & Neck Cancer, Immunotherapy. Dr. Thomas' major research goal is to conduct basic and translational studies to develop immunological approaches in the treatment of Head and Neck cancers. Elucidation of the role of the immune system in preventing progression of early Head & Neck cancers. Head and neck squamous cell carcinoma (HNSCC) of the upper aerodigestive tract is a devastating disease that impacts human communication and survival. Lack of effective immune responses is important in the progression of HNSCC, and is a prognostic marker for poor clinical response and decreased survival. The long-range goal of Dr. Thomas' research studies is to develop novel therapeutic modalities to improve anti-tumor immunity in patients with HNSCC, who continue to have disappointingly low survival rates despite aggressive treatments. The CD80/CD28 co-stimulation pathway is critical for T-cell activation and proliferation. It has been well documented in the literature that engagement of CD80 on antigen presenting cells by its receptor CD28 on T cells leads to multiple effects on immune responses in addition to increasing the synthesis of autocrine growth factors such as IL-2. To date, however, not much is known regarding the role of CD80 co-stimulatory molecules in generating anti-tumor immune responses against tumors formed from epithelial cells. Dr. Thomas' objective is to determine the role and regulation of CD80 co-stimulatory molecule during tumor progression of HNSCC. Her laboratory has previously characterized the expression of CD80 in different murine HNSCC clones derived naturally following tumor progression in the absence of T cell-mediated immunity in severe combined immune deficient (SCID) mice. One exciting feature observed during study was that HNSCC that did not express CD80 grew as progressors, while those that expressed CD80 were regressors when grown in immune competent animals. Preliminary data shows that CD80 mediated T-cell dependent anti-tumor immunity and the generation of protective immunity in animals resistant to rechallenge. In addition, they found that constitutive expression of one or more of the cytokines IL-1a, IL-6, and GM-CSF is associated with down-modulation of CD80 co-stimulatory molecule expression in oral HNSCC cells. The HNSCC cell lines that exhibit a combination of constitutive cytokine expression and low CD80 expression also exhibit increased tumorigenic potential in immune competent mice, as previously reported. Reduction of CD80 co-stimulatory molecule expression by pro-inflammatory cytokines IL-1a, IL-6, and GM-CSF has not been described previously. This decrease in CD80 expression during malignant progression of HNSCC may result in dysfunctional anti-tumor immunity, thereby promoting malignant growth. Studies are underway to determine the regulatory mechanisms of cytokine-induced down-regulation of CD80 expression and to determine the prognostic significance of its expression on tumor specimens from patients with HNSCC. Once the role and regulation of CD80 in HNSCC are understood, CD80 expression can be up-regulated pharmacologically in new and innovative approaches to increase anti-tumor immune responses for the prevention and treatment of HNSCC.