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. 2020 Oct;69(10):2089-2100.
doi: 10.1007/s00262-020-02604-w. Epub 2020 May 24.

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

Mario Sanchez-Canteli  1 , Rocio Granda-Díaz  1   2 , Nagore Del Rio-Ibisate  1   2 , Eva Allonca  1   2 , Fernando López-Alvarez  1   2 , Jackeline Agorreta  2   3 , Irati Garmendia  2   3 , Luis M Montuenga  2   3 , Juana M García-Pedrero  4   5   6 , Juan P Rodrigo  7   8   9
Affiliations

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

Mario Sanchez-Canteli et al. Cancer Immunol Immunother. 2020 Oct.

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.

Keywords: Head and neck cancer; PD-L1; Prognosis; Tumor-infiltrating lymphocytes.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Representative examples of positive PD-L1 expression in tumor and stromal immune cells (a), PD-1 expression in immune cells (b), high and low density of CD8+ TIL (c, d) and high and low density of FOXP3+ TIL (e, f). Original magnification X200
Fig. 2
Fig. 2
Correlations between PD-L1 tumor proportion score (TPS) and composite proportion score (CPS) and the density of CD8+ (a, b) and FOXP3+ TILs (c, d). Box plots with the median (black line) and the mean values are shown
Fig. 3
Fig. 3
Disease-specific survival (DSS) and overall survival (OS) curves categorized according to PD-L1 tumor proportion score (TPS; a, b), PD-L1 composite proportion score (CPS; c, d), CD8+ TIL density (e, f), FOXP3+ TIL density (g, h), and PD-1 expression (i, j)
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