Various threats are fought off by human defense mechanisms each day. These threats may be foreign, such as microbes, or endogenous, such as cancer cells. Since cancer cells are essentially the host’s own by origin, anti-cancer defense is a challenging task for the immune system.

This thesis work discusses the control of immunological responses, which may be dysregulated in the context of cancer, and the properties of cancer cells, which may determine their aggressiveness. This work focuses mainly on oral cavity squamous cell carcinoma. Special interest is shown to the Common Lymphatic Endothelial and Vascular Endothelial Receptor (Clever)-1, a scavenger receptor with multiple functions. Clever-1 is expressed in the tumor microenvironment of various solid tumors. Its inhibition by monoclonal antibodies or genetic deletion may inhibit tumor growth in mice. The exact mechanism by which Clever-1 targeting inhibits cancer growth is still incompletely understood. As a potential therapeutic target in cancer, its significance in normal immune responses demands investigation.

The first part of this thesis focused on the function of the humoral immune response in Clever-1 deficient settings. The work revealed vigorous humoral responses in Clever-1 deficient mice, in particular towards polysaccharide type antigens. Accelerated antibody responses should not subject the individual to immune-mediated adverse events; they may even contribute to the anti-cancer effects of Clever-1 blocking therapies.

The second part of my thesis project shows that high risk patients may be identified by immunohistochemical biomarkers. Clever-1 expression in these tumors was not clearly associated with clinicopathological parameters. Of the studied prognostic biomarkers, analysis of CD44 and Hypoxia Inducible Factor 1α allowed the identification of high risk patients, among unstratified patients with early stage OSCC.

In my work I discovered a new association between Clever-1 and humoral immunity. I also identified a potential way to prognosticate early stage OSCC patients.