Peripheral blood lymphocytes from patients with cancer lack interleukin-2 receptors

Abstract

When tumor cells develop in healthy adults, they activate the cellular immune system--natural killer (NK) cells, antigen-specific cytotoxic lymphocytes (CTL), and the synthesis of antigen specific cytotoxic antibodies. These are aimed at killing the intruding cells. However, in cancer patients the tumor continues to grow. As tumor cells proliferate, they were shown to release factors that mediate the inactivation of the host immune defense systems. The study documented in this article examined peripheral blood lymphocytes, mononuclear cells (MNC), NK cells, T-helper cells (THC). This study confirmed the interaction of the released inhibitor factors with these mononuclear cells. NULL cells from healthy adults responding to interleukin-2 (IL-2) and NILL cells from patients with metastatic breast carcinoma nonresponsive to IL-2 were also isolated by the standard antibodies-pinning technique. The cells were obtained from age-matched subjects: ten healthy adults; ten patients each from Stage I, II, III, and IV metastatic breast carcinoma (BCa-I, BCa-II, BCa-III, and BCa-IV or MBCa); and ten patients with benign breast disease (BBD). The responsiveness of these THC, PBMNC, NK, NULL, and NILL cells in vitro to graded levels of phytohemagglutinin (PHA), Concanavalin A (Con A), and recombinant interleukin-2 (rIL-2) was examined. Responsiveness was monitored by 3H-thymidine (3H-TdR) uptake, production and release of IL-2, interleukin-2 receptor (IL-2R), and cytotoxic activities against K-562 cells and breast carcinoma short-term cell lines. A lack of functional IL-2R in peripheral blood lymphocytes from patients with metastatic breast carcinoma was confirmed by nonsignificant anti-Tac antibody binding. An elevation in the expression of cell surface antigen GP-120 has been observed to be associated with the activation in vitro of T-cells from healthy adults and from patients with benign breast disease, but not of T-cells from patients with breast carcinoma. Biochemical studies of the GP-120 using high performance liquid chromatography combined with nitrocellulose blotting confirmed that the glycoprotein was resistant to trypsin and chymotrypsin, but susceptible to pronase. It contained sialic acid and lactosaminoglycan as O-linked sugars. It could be labeled with pariodate/NaB(3H4) and is recognized by MAbT-305 monoclonal antibodies. It contained sialic acid linked (2---3) to galactose.(ABSTRACT TRUNCATED AT 400 WORDS)