Differential expression of programmed cell death ligand 1 (PD-L1) and inflammatory cells in basal cell carcinoma subtypes

Arch Dermatol Res. 2022 Oct;314(8):777-786. doi: 10.1007/s00403-021-02289-w. Epub 2021 Oct 13.

Abstract

Few studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype.

Keywords: Basal cell carcinoma; Diagnosis; Immunohistochemistry; Immunotherapy; Lymphocytes; PD-1; PD-L1; Programmed cell death ligand 1; Stains.

MeSH terms

  • Aged
  • Apoptosis
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Basal Cell* / pathology
  • Female
  • Forkhead Transcription Factors
  • Humans
  • Ligands
  • Male
  • Retrospective Studies
  • Skin Neoplasms* / pathology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Forkhead Transcription Factors
  • Ligands