Analysis of types of Tumor-Infiltrating Immune Cells in Oral Squamous Cell Carcinoma (OSCC) and their associations with survival of OSCC patients.

Thesis (Master's)--University of Washington, 2017-06Background: The 5-year survival associated with oral cancer (OSCC) is relatively low. Recent investigations have implicated the presence of tumor infiltrating lymphocytes (TILs) as independent prognostic markers in several malignancies, including oral cancer. However, the studies of oral cancer evaluated only a limited number of immune cell types as prognostic markers. CIBERSORT, a computational software for in silico analysis of tumor microenvironment, provides an opportunity to measure 22 cell types of TILs in two previously-assembled cohorts of OSCC patients. Methods: We used CIBERSORT to evaluate Gene Expression Profiles (GEPs) of OSCC tumor samples using data from The Cancer Genomic Atlas (TCGA) and Fred Hutchinson Cancer Research Center’s Oralchip study to infer the types of immune cells that are present in the tumor tissue. Tumor samples were analyzed to evaluate a difference in immune cell composition of OSCC tumors by HPV status, location and by tumor stage. We also assessed the independent prognostic value of individual immune cell types by means of a multivariable Cox regression model which adjusted for patient’s age at diagnosis, HPV status, tumor location, tumor stage, and smoking and alcohol consumption history. In addition, we did a subset analysis on 50 HPV-positive oropharyngeal (OPC) cases where we assessed the independent prognostic value of individual immune cell types through the same multivariable Cox regression model. Results: The immune microenvironment of HPV-positive OSCC cases was significantly different compared to HPV-negative OSCC cases. The proportion of TILs such as naïve B cells, cytotoxic T cells, activated memory T cells, follicular helper and regulatory T cells was higher among HPV-positive OSCC cases and in HPV-positive OPC cases. Composition of some immune cell types differed by tumor stage. No significant association was observed between higher composition of individual immune cell types and overall survival in OSCC patients. Subset analysis showed that HPV-positive OPC cases with higher concentration of cytotoxic CD8+ T cells and activated memory CD4+ T cells were associated with better prognosis. On the other hand, higher concentrations of activated dendritic cells, mast cells and neutrophils were associated with relatively poor overall survival. Conclusion: Our study suggests immune system is predictive of survival in HPV-positive OPC patients, and that the composition of immune cells in HPV-positive OPC is different from that of HPV-negative OPC. These findings may help guide clinical management of these patients