Quantification of CD3, FoxP3, and granzyme B immunostaining in canine renal cell carcinoma

Vet Immunol Immunopathol. 2024 May:271:110741. doi: 10.1016/j.vetimm.2024.110741. Epub 2024 Mar 16.

Abstract

Tumor-infiltrating lymphocyte (TIL) density plays an important role in anti-tumor immunity and is associated with patient outcome in various human and canine malignancies. As a first assessment of the immune landscape of the tumor microenvironment in canine renal cell carcinoma (RCC), we retrospectively analyzed clinical data and quantified CD3, FoxP3, and granzyme B immunostaining in formalin-fixed paraffin-embedded tumor samples from 16 dogs diagnosed with renal cell carcinoma treated with ureteronephrectomy. Cell density was low for all markers evaluated. Increased numbers of intratumoral FoxP3 labelled (+) cells, as well as decreased granzyme B+: FoxP3+ TIL ratio, were associated with poor patient outcomes. Our initial study of canine RCC reveals that these tumors are immunologically cold and Tregs may play an important role in immune evasion.

Keywords: Cytotoxic T lymphocytes; Dog; Gamma-glutamyl transferase; T regulatory cells; Tumor-infiltrating lymphocytes.

MeSH terms

  • Animals
  • CD3 Complex* / analysis
  • CD3 Complex* / metabolism
  • Carcinoma, Renal Cell* / enzymology
  • Carcinoma, Renal Cell* / immunology
  • Carcinoma, Renal Cell* / veterinary
  • Dog Diseases* / enzymology
  • Dog Diseases* / immunology
  • Dogs
  • Forkhead Transcription Factors* / analysis
  • Forkhead Transcription Factors* / metabolism
  • Granzymes* / analysis
  • Granzymes* / metabolism
  • Immunohistochemistry / veterinary
  • Kidney Neoplasms* / enzymology
  • Kidney Neoplasms* / immunology
  • Kidney Neoplasms* / veterinary
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Retrospective Studies

Substances

  • CD3 Complex
  • Forkhead Transcription Factors
  • Granzymes