The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs).
Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment.
29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL).
High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.
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This study was supported by Grants from the Plan Nacional de I+D+I 2013–2016 [ISCIII (PI16/00280 and PI19/00560 to JMGP and PI19/00098 to LMM), CIBERONC (CB16/12/00390 to JPR and CB16/12/00443 to LMM)], the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Fundación Merck Salud (17-CC-008 to JPR), Ayudas a Grupos PCTI Principado de Asturias (IDI2018/155 to JPR), and the FEDER Funding Program from the European Union. RGD is recipient of a Severo Ochoa predoctoral fellowship (BP19-063) from the Principado de Asturias, and NRI is recipient of a FPU predoctoral fellowship (FPU17/01985) from the Spanish Ministry of Education. We want to particularly acknowledge for its collaboration the Principado de Asturias BioBank (PT17/0015/0023), financed jointly by Servicio de Salud del Principado de Asturias, Instituto de Salud Carlos III, and Fundación Bancaria Cajastur and integrated in the Spanish National Biobanks Network.
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The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee [Regional Ethical Committee from Principado de Asturias for the project PI16/00280 (approval number: 70/16; date: 5 May 2016)] and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Sanchez-Canteli, M., Granda-Díaz, R., del Rio-Ibisate, N. et al. PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas. Cancer Immunol Immunother 69, 2089–2100 (2020). https://doi.org/10.1007/s00262-020-02604-w
- Head and neck cancer
- Tumor-infiltrating lymphocytes