Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis.
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 wer...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000889 |
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| author | FJ Mulder EJ de Ruiter TFB Gielgens F Farshadpour R de Bree MFCM van den Hout B Kremer SM Willems EJM Speel |
| author_facet | FJ Mulder EJ de Ruiter TFB Gielgens F Farshadpour R de Bree MFCM van den Hout B Kremer SM Willems EJM Speel |
| author_sort | FJ Mulder |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-902b8a3231864052b7f25c33b6e67d80 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-902b8a3231864052b7f25c33b6e67d802025-08-20T02:09:40ZengElsevierTranslational Oncology1936-52332025-05-015510235710.1016/j.tranon.2025.102357Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis.FJ Mulder0EJ de Ruiter1TFB Gielgens2F Farshadpour3R de Bree4MFCM van den Hout5B Kremer6SM Willems7EJM Speel8Department of Otorhinolaryngology and Head & Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands; Corresponding author.Department of Pathology, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Otorhinolaryngology, Amsterdam University Medical Center, Amsterdam, NetherlandsDepartment of Otorhinolaryngology, BovenIJ Hospital, Amsterdam, NetherlandsDepartment of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, NetherlandsDepartment of Otorhinolaryngology and Head & Neck Surgery, Erasmus Medical Center, Rotterdam, NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, Groningen, NetherlandsDepartment of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, NetherlandsObjectives: 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.http://www.sciencedirect.com/science/article/pii/S1936523325000889Head and neck cancerProgrammed death ligand 1Tumor infiltrating lymphocytesNon-smokersNon-drinkers |
| spellingShingle | FJ Mulder EJ de Ruiter TFB Gielgens F Farshadpour R de Bree MFCM van den Hout B Kremer SM Willems EJM Speel Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. Translational Oncology Head and neck cancer Programmed death ligand 1 Tumor infiltrating lymphocytes Non-smokers Non-drinkers |
| title | Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. |
| title_full | Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. |
| title_fullStr | Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. |
| title_full_unstemmed | Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. |
| title_short | Frequent PD-L1 expression in oral squamous cell carcinoma of non-smokers and non-drinkers, and association of tumor infiltrating lymphocytes with favorable prognosis. |
| title_sort | frequent pd l1 expression in oral squamous cell carcinoma of non smokers and non drinkers and association of tumor infiltrating lymphocytes with favorable prognosis |
| topic | Head and neck cancer Programmed death ligand 1 Tumor infiltrating lymphocytes Non-smokers Non-drinkers |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000889 |
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