Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

Clin Exp Immunol. 1997 Sep;109(3):501-9. doi: 10.1046/j.1365-2249.1997.4771375.x.

Abstract

We investigated the phenotype and functional capacities of tumour-infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n = 20). Three-colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3+ T cells, with a clear predominance of CD4- CD8+ over CD4+ CD8- T cells, and a marked population of CD4+ CD8+ T cells. Natural killer (NK) cells were also strongly represented (> 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (< 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA-DR was also elevated on CD3+ TIL, and HLA-DR expression was further vigorously up-regulated following ex vivo stimulation with anti-CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3+ CD4+ TIL displayed a normal capacity to up-regulate CD25 expression and to secrete both Th1-type (IL-2, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)) and Th2-type (IL-4, IL-5 and IL-10) cytokines upon triggering with anti-CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3+ CD8+ TIL, on the other hand, consistently demonstrated a poor up-regulation of CD25 upon triggering with anti-CD3, and displayed poor ex vivo cytolytic activity in an anti-CD3-redirected 4-h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3+ CD4+ TIL in RCC have normal functional capacities, whereas the proportionally major CD3+ CD8+ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Antigens, CD / analysis
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / immunology
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique, Direct
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / immunology*
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD3 Complex
  • HLA-DR Antigens
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma