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PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas

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Abstract

Introduction

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).

Methods

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.

Results

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).

Conclusions

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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Acknowledgements

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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Authors and Affiliations

  1. Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain

    Mario Sanchez-Canteli, Rocio Granda-Díaz, Nagore del Rio-Ibisate, Eva Allonca, Fernando López-Alvarez, Juana M. García-Pedrero & Juan P. Rodrigo

  2. Ciber de Cáncer, CIBERONC, 28029, Madrid, Spain

    Rocio Granda-Díaz, Nagore del Rio-Ibisate, Eva Allonca, Fernando López-Alvarez, Jackeline Agorreta, Irati Garmendia, Luis M. Montuenga, Juana M. García-Pedrero & Juan P. Rodrigo

  3. Program in Solid Tumors, Center for Applied Medical Research (CIMA), Department of Pathology, Anatomy and Physiology, University of Navarra and Navarra’s Health Research Institute (IDISNA), 31008, Pamplona, Spain

    Jackeline Agorreta, Irati Garmendia & Luis M. Montuenga

  4. Lab ORL, Edificio FINBA, Hospital Universitario Central de Asturias, Avda Roma s/n 33011, Oviedo, Spain

    Juana M. García-Pedrero & Juan P. Rodrigo

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  1. Mario Sanchez-Canteli
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  2. Rocio Granda-Díaz
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  3. Nagore del Rio-Ibisate
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Contributions

JPR and JMGP were involved in the conceptualization; MSC, RGD, NRI, EA, JA, and IG contributed to methodology; JPR, JMGP, FLÁ, and LMM helped in formal analysis and investigation; JPR was involved in writing—original draft preparation; JMGP, FLÁ, and LMM contributed to writing—review and editing; JPR, JMGP, and LMM helped in funding acquisition; JPR and LMM contributed to resources; JPR, JMGP, and LMM helped in the supervision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Juana M. García-Pedrero or Juan P. Rodrigo.

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The authors declare that they have no conflict of interest.

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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

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