HPV-driven immune modulation in oropharyngeal squamous cell carcinoma

Introduction:

Increasing rates of oropharyngeal squamous cell carcinoma (OPSCC) are related to human papilloma virus (HPV) and viral induced immune modulation is expected. LAG3 expression on regulatory T-cells and MHCI loss on carcinoma cells are designated to contribute to an immunosuppressive tumor microenvironment. The purpose of this study was to analyze the prognostic relevance of LAG3-, MHCI expression and tumor infiltrating lymphocytes in OPSCC in accordance to HPV-status.

Methods:

We created a tissue micro array of paraffin embedded tumor tissue of 264 patients with OPSCC. HPV-status was determined retrospectively by p16-immunohistochemistry and HPV-DNA detection. LAG3, CD3 and CD8 expression on lymphocytes and MHCI on tumor cells were evaluated and statistically analyzed.

Results:

LAG3 expression was detected more often in HPV+ OPSCC than in HPV- cases (44,4% vs. 25,6%) and patients with LAG3 expression had a better overall survival independent of HPV-status (p = 0,032). HPV-associated OPSCC showed an intratumoral T-lymphocyte-rich inflammatory microenvironment more frequently (p < 0,001) and this was associated with improved survival (p < 0,001). MHCI loss was found more often in HPV-associated tumors but had no significant impact on survival in the entire cohort or according to HPV-status.

Conclusions:

In our cohort, expression of LAG3 indicates a favorable outcome showing the importance of immunomodulation in OPSCC. Our data suggest an impact of LAG3 and MHCI on anti-tumoral T-cell effector infiltration in OPSCC and this might therefore serve as a prognostic factor.

Publication History

Publication Date:
23 April 2019 (online)