Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

Abstract

SUMMARYFresh (uncultured) TIL from 12 untreated patients with primary renal cell carcinoma were prepared from tumour specimens by enzymatic digestion, and were characterized by immunotluorescence using MoAbs recognizing leucocyte differentiation antigens or particular Va or V/? segments of the T cell receptor (TCR). These fresh TIL comprised CD3+ (20-84%); CD4+ (3-15%); CD8+ (13-35%); a/3TCR^ (20 50%); 7<5TCR+ (3-17%); CD16+ (1-18%) and CD56( 3-10%) cells. Significant proportions of VQ2"', V^5.1+ and V^6+ cells were found in TIL of certain patients with renal cell carcinoma, suggesting that they comprised oligoclonal T cells. T cell lines were developed in low concentrations of rIL-2 (200 U/ml) from TIL from II patients wiih renal cell carcinoma, and were characterized by immunofluorescence and cell-mediated cytotoxicity. These T cell lines consisted primarily of CD3^ (51-94%); CD4+ (1 80%); CD8+ (0-84%); Q/3TCR+ (65-87%); 7^TCR+ (0-25%); CDI6+ (0-16%) and CD56+ (2-57%) cells. These Tcell lines exhibited non-specific cytotoxicity against autologous and aliogeneic renal tumour cells, with the exception of one T cell line that exhibited preferential cytotoxicity against autoiogous renal tumour cells. These results suggest that fresh TIL from patients with renal cell carcinoma contain significant proportions of oligoclonal T cells that may have accumulated at the tumour site as a result ofa clonal expansion.

Localization of T cell receptor (TCR)- γδ+ T cells into human colorectal cancer: flow cytometric analysis of TCR-γδ expression in tumour-infiltrating lymphocytes

“…It has been reported recently that TIL in advanced pancreatic cancer included a higher percentage of 7^ T cells than PBL [12]. However, previous examinations of other types of human solid tumours, for example, renal cell carcinoma, primary liver tumour, breast cancer, and dysgerminoma of the ovary, have shown similar results, in that the frequencies of TCR-7(^ expression in freshly isolated TIL were low [13][14][15][16]. We compared this frequency, for the first time, between malignant and normal tissues of the same patient, and confirmed the conclusion that TCR-7(S' T cells are present in the tumour at relatively low levels.…”

Cell transfer regimens in patients with highly advanced surgically unresectable non-small cell lung cancer: Significantly improved overall survival in patients with lower levels of serum immunosuppressive acidic protein

“…Our study shows that after a 12-day culture, LAK cells (a majority being ␥␦T cells), when briefly exposed to IFN-␣, demonstrated enhanced cytotoxicity against Daudi cells [10] as well as K562 cells. Our recent studies determined that these IFN-␣ activated LAK cells (BAK cells) contain high numbers of phenotypically distinct CD4 − CD8 − CD56 + CD69 + TCR␥␦T cell subsets that have strong lytic activities against a wide variety of autologous tumor cells from diverse origins [9,[36][37][38]. It is speculative that, after intravenous delivery, the IFNactivated CD69 + ␥␦T cells may be efficiently recruited towards the tumor sites.…”

Phenotype Analysis of Tumour-infiltrating Lymphocytes and Lymphocytes in Peripheral Blood in Patients with Renal Carcinoma

“…The significance of the role of antigen-presenting cells was not unambiguously proven in tumour diseases in case of B lymphocytes (3,21,26,32,33). In our patients, B lymphocytes were less than 1 % of TILs and their numbers were significantly lower compared to their numbers in PBL.…”