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.
