PD-L1 Expression, T-lymphocyte Subpopulations and Langerhans Cells in Cutaneous Squamous Cell Carcinoma and Precursor Lesions

Anticancer Res. 2021 Jul;41(7):3439-3448. doi: 10.21873/anticanres.15131.

Abstract

Background/aim: The role of immune cells and PD-L1 in cutaneous squamous carcinogenesis is unclear. This study examines T-cell populations, Langerhans cells (LCs) and PD-L1 in invasive squamous cell carcinoma (inSCC), adjacent precursors and normal skin (NS) to investigate their participation in tumorigenesis.

Materials and methods: Cases of cutaneous inSCC with adjacent precursors (n=125) were selected. In situ SCC (isSCC) and actinic keratosis (AK) were observed in 53 and 123 cases, respectively, whereas NS was present in 123 lesions. Immunohistochemistry was performed for CD3, CD8, Foxp3, CD1a and PD-L1.

Results: T-cells, LCs and PD-L1 gradually increase during the evolution from AK to isSCC and inSCC, with statistical significance between all lesions, except for CD3+ and CD8+ cells between isSCC and inSCC. Epithelial PD-L1 expression correlates with tumor diameter and thickness.

Conclusion: The progressive increase of T-cells, LCs and PD-L1 in cutaneous squamous carcinogenesis provides rationale for immunotherapy and identification of predictive biomarkers.

Keywords: Cutaneous invasive squamous cell carcinoma; Langerhans cells; actinic keratosis; in situ squamous cell carcinoma; programmed death-ligand 1/PD-L1; tumor infiltrating lymphocytes/TILs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism*
  • Langerhans Cells / pathology
  • Male
  • Middle Aged
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CD3 Complex