The expression of immune checkpoint proteins PD-L1 and TIM3 in mouse and human head and neck squamous cell carcinoma

Eur J Oral Sci. 2024 Oct;132(5):e13010. doi: 10.1111/eos.13010. Epub 2024 Aug 1.

Abstract

The aim of this study was to examine the expression of programmed death-ligand 1 (PD-L1) and of T cell immunoglobulin and mucin domain-containing protein (TIM3) in oral epithelial dysplasia and head and neck squamous cell carcinoma (HNSCC). Mouse HNSCC was induced with 4-nitroquinoline-1 oxide (4NQO). Oral epithelial dysplastic lesions, carcinoma in situ and HNSCC lesions were stained with anti-PD-L1 and TIM3 antibodies. The expression of PD-L1 and TIM3 in tumor cells and immune cells was semiquantitatively measured and compared. In parallel, human dysplasia and HNSCC were stained with anti-PD-L1 and anti-TIM3. The expression pattern of PD-L1+ and TIM3+ cells was further compared. In human and mouse samples both PD-L1 and TIM3 were found to be expressed in neoplastic and immune cells in HNSCC, but not in dysplasia. There was no significant difference in PD-L1 and TIM3 expression between metastatic and nonmetastatic HNSCC. We conclude that the 4NQO-induced mouse HNSCC model may be an excellent preclinical model for immune checkpoint therapy.

Keywords: head and neck squamous cell carcinoma; immune checkpoint proteins; immunotherapy.

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • B7-H1 Antigen* / metabolism
  • Female
  • Head and Neck Neoplasms* / immunology
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Hepatitis A Virus Cellular Receptor 2* / metabolism
  • Humans
  • Mice
  • Squamous Cell Carcinoma of Head and Neck* / immunology
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • B7-H1 Antigen
  • HAVCR2 protein, human
  • 4-Nitroquinoline-1-oxide
  • CD274 protein, human
  • Havcr2 protein, mouse