Human accessory cells activate fresh, normal, tumor-distant T lymphocytes but not tumor-infiltrating T lymphocytes to lyse autologous tumor cells in a primary cytotoxic T lymphocyte assay in renal cell carcinoma.
OBJECTIVE
Search for an ideal responder T-lymphocyte source for adoptive T-lymphocyte therapy in renal cell carcinoma (RCC).


METHODS
Cytotoxic T-lymphocyte (CTL) activity of (a) normal, tumor-distant, renal T lymphocytes, (b) tumor-infiltrating T lymphocytes and (c) peripheral blood T lymphocytes against autologous tumor epithelial cells (EC) of 10 patients with organ-confined, primary RCC was analyzed in a primary CTL assay. Freshly enriched T lymphocytes were cultured with or without autologous, mitomycin-C-treated normal or tumor EC in the presence or absence of antigen-presenting cells (APC) for 7 days.


RESULTS
Both tissue T-lymphocyte populations displayed a similar CD4:CD8 ratio (1:1). Elevated CD62L coexpression of CD4+ T lymphocytes in normal, tumor-distant, renal tissue resulted in a significantly higher transient T-cell activation than that seen in renal tumor tissue (46 vs. 27%; p = 0.002). All trials to induce significant lysis of autologous, renal tumor EC in tumor-infiltrating and peripheral blood T lymphocytes failed. Only when normal, tumor-distant, renal T lymphocytes were stimulated by autologous APC and tumor EC was significant autologous tumor EC lysis obtained (mean 14%; p<0.05). Costimulation by anti-CD3 (mean 21%; p<0.05) or interleukin-2 (mean 31%; p<0.05) further increased tumor EC lysis significantly.


CONCLUSIONS
Increased turnover of T lymphocytes in normal, tumor-distant, renal tissue was associated with a higher yield of pre-CTL which can be transformed into a functionally active effector T-cell pool by stimulation via antigen plus APC. Thus, tumor-distant renal tissue has to be included in the tissue-sampling procedure for adoptive immunotherapy.
Kramer
G
G
Department of Urology, University of Vienna, Austria. uroldep@akh-wien.ac.at
Steiner
G E
GE
Paiha
S
S
Handisurya
A
A
Djavan
B
B
Mallone
R
R
Marberger
M
M
D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured