Quantitation of proliferative and cytotoxic precursor cells directed against human tumours: limiting dilution analysis in peripheral blood and at the tumour site.

Abstract

Blood and tumour-infiltrating lymphocytes (TIL) from 16 cancer patients have been examined under limiting dilution conditions to determine the frequency of cells responding in mixed tumour-lymphocyte cultures (MLTC) to autologous tumour and Interleukin-2 (IL-2). Tumour-derived lymphocytes showed a high spontaneous response to IL-2 alone 1/1,900 in TIL; 1/6,000 in PBL suggesting the presence of "activated" T cells in situ. Proliferative frequencies were increased in MLTC in both blood (1/3,779) and TIL (1/1,084). Phenotypic analyses showed that total T-cell contents of the responder populations were comparable but TIL were enriched for the OKT8+ subset with a corresponding reduction in OKT4+. TIL showed increased numbers of OKMI+ and Tac+ lymphocytes. The major cytotoxic precursor expanding under these conditions was reactive against autologous tumour. K562 (NK) were present at a lesser frequency--particularly in TIL. The data show a concentration and activation of reactive lymphocytes at the tumour site and establish conditions for the clonal expansion of specifically cytotoxic T cells.