The immune microenvironment in oral squamous cell carcinoma – characterization and prognostic markers

Abstract

Oral squamous cell carcinomas (OSSCs) are aggressive tumors often associated with a low survival rate. The immune system influences the development of OSCCs, and the immune infiltrate surrounding the cancer cells is an indicator of the host’s anti-tumor response. The main aim of this thesis was to describe how the tumor microenvironment in OSCC is organized, and to determine whether different subsets of the immune infiltrate can be used to predict patient outcome. In tissue from 80 OSCC patients, we used immunohistochemistry to detect distinct cellular components of the immune infiltrate. In addition, we used qPCR to analyze the gene expression of a number of inflammation-related cytokines and chemokines. We correlated the presence of the various components to each other as well as to clinicopathological data and the patients’ survival. A systematic review of the literature was conducted to identify promising prognostic factors in OSCC and to evaluate the quality of the published studies. In our review, we found that CD163+ M2 macrophages and CD57+ mature natural killer cells were the most promising prognostic markers and that the data reported in the papers was often incomplete. In our Norwegian OSCC patient cohort, the presence of specialized blood vessels called high-endothelial venules (HEVs) was a reliable, easy-to-use, independent prognostic marker for improved survival and had the most promising potential of the factors analyzed. However, larger, standardized studies are needed to reliably conclude about the prognostic value of the markers identified in our Norwegian OSCC cohort and our literature review. HEVs are known to be gateways for lymphocyte entry to the tumor site. We found HEVs to be associated with a potentially tumor-suppressive immune microenvironment. Therefore, we hypothesize that HEVs may be master regulators of a favorable immune reaction and potential targets for immune-modulating therapies.