Immune surveillance of nasopharyngeal carcinoma (NpC).

Abstract

In the U.S., nasopharyngeal carcinoma (NpC) kills >7,600 each year. Deaths are predominantly among adult men, and in most cases, early detection and treatment can save lives. Despite the annual spending of approximately 3.2 billion dollars on head and neck cancer research, NpC remains a neglected disease since its fatality rates are among the lowest nation wide. The relative survival rates from NpC have not improved in the U.S. in the last 20 years. Infection with Epstein Barr Virus (EBV) is an important co-factor in the etiology of NpC. In other regions of the word (e.g., South-East Asia, Latin America), EBV infection and NpCrelated prevalence and mortality are substantially higher and more alarming. Epidemiological data indicate high prevalence of EBV infection and increased risk for NpC among Central and South American and Asian immigrants in the U.S., and also predict a sharp increase in NpC incidence in the next decade. To face this emerging threat, it is important to develop and validate novel modes of detection and intervention for NpC. To this end, we characterized the proteomic signature of NpC, and of the tumor infiltrating lymphocytes of the CD8+, activated (CD38+, mTOR+) and regulatory immune cell (FoxP3+) phenotype. Paraffinized biopsies were processed, and tissue microarrays constructed and tested by immunohistochemistry and triimmunohistofluorescence for a battery of signaling markers, including AKT and PI3K, in conjunction with EBV status and ANKRD11, an NpC susceptibility biomarker. Microphotographs, analyzed and quantified by confocal microscopy and fractal analysis, suggest new avenues for immunotherapies of NpC.