Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma.

PURPOSE This study examines the tumour-host immune interactions in head and neck squamous cell carcinoma (HNSCC) and their relationship to human papillomavirus (HPV) infectivity and patient survival. METHODS The adaptive and innate immune profile of surgical tumour specimens obtained from HNSCC patients was determined using qRT-PCR and immunohistochemistry. Intratumoural and invading margin leukocyte populations (CD3, CD8, CD16, CD20, CD68, FoxP3 and HLA-DR) were quantified and compared with patient disease-specific survival. Additionally, the expression of 41 immune activation- and suppression-related genes was evaluated in the tumour microenvironment. Tumour cells were also assessed for expression of HLA-A, HLA-G and HLA-DR. HPV infectivity of tumour biopsies was determined using HPV consensus primers (MY09/MY11 and GP5+/GP6+) and confirmed with p16 immunohistochemistry. RESULTS HPV+ patient samples showed a significantly increased infiltration by intratumoural CD20+ B cells, as well as by invasive margin FoxP3+Treg, compared with HPV- patient samples. There was also a trend towards increased intratumoural CD8+ T cells and HLA-G expression on tumour cells in HPV+ samples. qRT-PCR data demonstrated a general pattern of increased immune activation and suppression mechanisms in HPV+ samples. Additionally, a combined score of intratumoural and invasive margin FoxP3 infiltration was significantly associated with disease-specific survival (P < 0.05). CONCLUSIONS These data demonstrate significant differences in the immune cell profile of HPV+ and HPV- HNSCC. This study identifies several possible targets for immunotherapy and possible prognostic markers (FoxP3 and HLA-G) that may be specific to HNSCC.