CD56‐positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma. Issue 9 (8th January 2016) - Wagner, Steffen
Abstract : Human papillomavirus (HPV)‐related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV‐unrelated counterparts. Patients with HPV‐related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead‐based hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV‐DNA. We found significantly higher numbers of CD56 positive (CD56+) cells in tumor and surrounding microenvironment in HPV‐associated compared to HPV‐negative OSCC ( t ‐test: p = 0.004 and p = 0.002). For the entire cohort presence of CD56+ cells was associated with increased overall survival independent from HPV (Kaplan–Meier: p = 0.002; Cox regression: p = 0.042). Presence of CD56+ cells also correlated with a better outcome in HPV‐negative and especially in HPV‐negative OSCC with alcohol consumption ≤2 standard drinks per day (Kaplan–Meier: p = 0.05 and p = 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD56+ cells and coexpression of CD16 and CD56 suggests that detected CD56+ cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV‐associated compared to HPV‐negative OSCC (Mann‐Whitney‐U‐Test: p = 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV‐related OSCC. Abstract : What's new? Human papillomavirus (HPV)‐related squamous cell carcinoma of the oropharynx (OSCC) are clinically and biologically distinct from HPV‐unrelated OSCC. Here, the authors set to explore whether immune cells contribute to the improved prognosis of patients with HPV‐associated compared to HPV‐negative OSCC. For the first time, they report the presence of CD56+ cells to be an independent predictor for better survival of patients with OSCC. In particular, higher CD56+ cell numbers and potentially cytotoxic CD56+ cell frequencies were associated with HPV‐related OSCC. Activated Natural Killer cells may thus contribute to improved outcome in HPV‐related, and also in a subset of HPV‐negative, OSCC.