PD‐L1 expression in tumour‐infiltrating lymphocytes is a poor prognostic factor for primary acral melanoma patients

• Published in: Histopathology Vol. 73; no. 3; pp. 386 - 396
• Main Authors: Ren, Min, Dai, Bo, Kong, Yun‐Yi, Lv, Jiao‐Jie, Cai, Xu
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2018
• Subjects: acral melanoma; Adult; Aged; Apoptosis; B7-H1 Antigen - analysis; B7-H1 Antigen - biosynthesis; Biomarkers, Tumor - immunology; Cell death; Disease-Free Survival; Female; Humans; Immunohistochemistry; Immunotherapy; Kaplan-Meier Estimate; Lymphocytes; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medical prognosis; Melanoma; Melanoma - mortality; Melanoma - pathology; Metastases; Middle Aged; Multivariate analysis; PD-L1 protein; PD‐L1; Prognosis; prognostic factor; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Stroma; Tumors; tumour‐infiltrating lymphocytes; PD-L1; acral melanoma; immunohistochemistry; prognostic factor; tumour-infiltrating lymphocytes
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13527

Aims Programmed cell death protein 1–programmed death‐ligand 1 (PD‐L1) blockade immunotherapy has shown notable therapeutic benefit in metastatic melanoma, but the clinical relevance of PD‐L1 expression remains unclear in melanoma, especially in acral melanoma, which is the most common subtype in Asians. The aim of this study was to evaluate the clinical effect of PD‐L1 expression in primary acral melanoma. Methods and results We used immunohistochemistry to evaluate PD‐L1 expression in tumour cells and tumour‐infiltrating lymphocytes (TILs), and analysed its associations with clinicopathological features and survival in 78 primary acral melanoma patients. We found that expression of PD‐L1 in tumour cells and TILs occurred exclusively in a tumour–stroma interface pattern, consistent with the predominant pattern of TIL distribution. The presence of peritumoral TILs was also associated with high PD‐L1 expression in tumour cells. Furthermore, PD‐L1 expression in tumour cells and that in TILs showed a close relationship (Spearman's rho = 0.381, P = 0.001). However, neither PD‐L1 expression in tumour cells nor that in TILs was significantly correlated with clinicopathological features. In univariate analysis, cases with PD‐L1‐positive TILs had significantly poorer survival than those with PD‐L1‐negative TILs (median disease‐specific survival of 40.7 months versus 78.0 months; P = 0.008). In multivariate analysis, PD‐L1 expression in TILs was an independent factor for poor prognosis (P = 0.032), whereas PD‐L1 expression in tumour cells was not significantly correlated with survival in univariate analysis (P = 0.378) and multivariate analysis (P = 0.354). Conclusion This is the first study to demonstrate that PD‐L1 expression in TILs, but not that in tumour cells, is an independent predictor of poor prognosis in acral melanoma.