Premium
Peripheral blood lymphocytes from patients with cancer lack interleukin‐2 receptors
Author(s) -
Hakim Anwar A.
Publication year - 1988
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19880215)61:4<689::aid-cncr2820610412>3.0.co;2-o
Subject(s) - cytotoxic t cell , peripheral blood mononuclear cell , immunology , immune system , medicine , population , antigen , antibody , interleukin 2 , cancer , cancer research , biology , in vitro , biochemistry , environmental health
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 NULL and NILL cell populations were obtained after panning of all known cell types. The identity of this cell population is heterogeneous and uncommitted. Because the type of the cell population from healthy adults could vary from that obtained from patients with BCa, in this study they are referred as NULL and NILL, respectively. To establish the exact identity of these cells, monoclonal antibodies to both NULL and NILL cell populations is in progress. 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 2 H‐thymidine ( 3 H‐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( 3 H 4 ) and is recognized by MAbT‐305 monoclonal antibodies. It contained sialic acid linked (2—3) to galactose. The ability of MAbT‐305 to inhibit the proliferative response to mitogens and IL‐2 in lymphocytes from healthy adults, but without any effect on PBL from patients with breast carcinoma at various pathologic stages confirms that the expression of the IL‐2R function is defective.