PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head
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ORIGINAL ARTICLE
PD‑L1 expression correlates with tumor‑infiltrating lymphocytes and better prognosis in patients with HPV‑negative head and neck squamous cell carcinomas Mario Sanchez‑Canteli1 · Rocio Granda‑Díaz1,2 · Nagore del Rio‑Ibisate1,2 · Eva Allonca1,2 · Fernando López‑Alvarez1,2 · Jackeline Agorreta2,3 · Irati Garmendia2,3 · Luis M. Montuenga2,3 · Juana M. García‑Pedrero1,2,4 · Juan P. Rodrigo1,2,4 Received: 28 December 2019 / Accepted: 12 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 F OXP3+ 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 diseasespecific 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. Keywords Head and neck cancer · PD-L1 · Tumor-infiltrating lymphocytes · Prognosis
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02604-w) contains supplementary material, which is available to authorized users. * Juana M. García‑Pedrero [email protected]
It is now recognized that the immune system plays a key role in the development and progression of cancers [1], including the head and neck squamous cell carcinomas 2
Ciber de Cáncer, CIBERONC, 28029 Madrid, Spain
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
4
Lab ORL, Edificio FINBA, Hospita
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