PD-L1 and LAG-3 expression in advanced cutaneous squamous cell carcinomas

J Cutan Pathol. 2020 Oct;47(10):882-887. doi: 10.1111/cup.13709. Epub 2020 Jun 11.


Background: Expression of programmed death ligand 1 (PD-L1) by cutaneous squamous cell carcinomas has been shown to correlate with advanced disease and risk of metastasis. Lymphocyte activation gene 3 (LAG-3, or CD223) is an inhibitory receptor that interacts with the PD-L1 axis, which has been shown to be a marker of immune exhaustion and a potential immunotherapy target. However, the role of LAG-3 in cutaneous squamous cell carcinoma has not been established.

Methods: We reviewed 18 cases of locally advanced and/or metastatic cutaneous squamous cell carcinomas and assessed for PD-L1 expression, presence or absence of tumor-infiltrating lymphocytes (TILs), and expression of LAG-3 by TILs.

Results: PD-L1 expression was present in 11 of 13 locally advanced primary tumors and 5 of 5 metastases. TILs were present in all 18 tumors, of which 14 cases were positive for LAG-3 expression. In positive cases, LAG-3 was expressed on average by 32% of TILs.

Conclusions: Advanced cutaneous squamous cell carcinomas frequently express PD-L1 and are associated with an inflammatory response. LAG-3 expression by TILs was identified in a majority of cases. Our findings suggest that LAG-3 positive tumor-associated inflammatory cells may play a role in the development of advanced disease and offer another potential target for drug therapy.

Keywords: LAG-3; PD-L1; immunotherapy; squamous cell carcinoma; tumor-infiltrating lymphocytes.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism*
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / secondary
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy / methods
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / pathology
  • Neoplasm Staging
  • Skin Neoplasms / pathology*
  • Tumor Microenvironment / immunology


  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human