Work

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

Year: 2025

Type: article

Abstract: • >85 % of OSCC in non-smokers and non-drinkers show PD-L1 expression (CPS ≥1). • There are frequent high CD8-positive TIL infiltrates in PD-L1-positive OSCC. • CD4-positive TILs predict disease free survival and overall survival. 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). 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/mm 2 . 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. 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+. 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.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102357