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

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2025-03-15 DOI:10.1016/j.tranon.2025.102357
FJ Mulder , EJ de Ruiter , TFB Gielgens , F Farshadpour , R de Bree , MFCM van den Hout , B Kremer , SM Willems , EJM Speel
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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.
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材料与方法回顾性收集了86名患有口腔鳞状细胞癌(OSCC)的NSND患者的临床特征和肿瘤组织,并通过组织芯片分析其蛋白质表达。对 PD-L1 CPS、PD-L2 TPS 和 PD-1、CD45、CD8、CD4、CD3 和 FoxP3 阳性 TILs/mm2 的表达进行免疫组化。使用 QuPath 对切片进行数字评估。5 年 DFS 和 OS 的差异通过对数秩分析确定。结果88%(76/86)的OSCC显示PD-L1表达(CPS≥1)。CD4阳性TIL数量多的患者的DFS和OS均优于CD4阳性TIL数量少的患者。在最佳多变量模型中,CD4阳性TIL也是DFS(p = 0.010)和OS(p = 0.002)的独立预测因子。此外,CD45阳性TIL数量多、CD8/FoxP3比值高的患者OS较好,其中CD8/FoxP3比值是近乎显著的独立预测因子(p = 0.050)。结论 NSND中大量OSCC显示PD-L1表达(CPS≥1)。CD4是DFS和OS的重要预测因子,此外CD8/FoxP3比值也是OS的近似重要预测因子。PD-L1阳性肿瘤中经常出现高CD8阳性TIL浸润,这使得患有OSCC的NSND患者在理论上成为免疫检查点抑制剂治疗的理想候选者。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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