Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis.

Abstract

Objectives

To determine the presence and prognostic value of PD-L1 and PD-L2 expression, and tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC) of non-smokers and non-drinkers (NSND).

Materials and methods

Clinical characteristics and tumor tissue of 86 NSND with OSCC were retrospectively collected and analyzed for protein expression on tissue microarrays. Immunohistochemistry was performed for expression of PD-L1 CPS, PD-L2 TPS, and PD-1, CD45, CD8, CD4, CD3, and FoxP3-positive TILs/mm². Slides were digitally evaluated using QuPath. Differences in 5-year DFS and OS were determined by log rank analysis. Predictors for survival were determined by multivariable cox regression analysis.

Results

Eighty-eight percent (76/86) of OSCC showed PD-L1 expression (CPS ≥1). Patients with high numbers of CD4-positive TILs showed a better DFS and OS than patients with low numbers of CD4-positive TILs. In the best multivariable model, CD4-positive TILs were an independent predictor for DFS (p = 0.010) and OS (p = 0.002) too. Additionally, patients with high numbers of CD45-positive TILs and a high CD8/FoxP3 ratio showed a better OS, of which the CD8/FoxP3 ratio was a near significant independent predictor (p = 0.050). Over 40 % of OSCC were PD-L1+/TIL+.

Conclusion

A large number of OSCC in NSND show PD-L1 expression (CPS ≥1). CD4 was a significant predictor for DFS and OS, in addition to the CD8/FoxP3 ratio being a near significant predictor for OS. The combination of frequent high CD8-positive TIL infiltrates in PD-L1-positive tumors makes NSND with OSCC in theory interesting candidates for treatment with immune checkpoint inhibitors.