Modulations of the effector function and cytokine production of human lymphocytes by secreted factors derived from colorectal-carcinoma cells
- PMID: 9212235
- DOI: 10.1002/(sici)1097-0215(19970703)72:1<142::aid-ijc20>3.0.co;2-k
Modulations of the effector function and cytokine production of human lymphocytes by secreted factors derived from colorectal-carcinoma cells
Abstract
We investigated the in vitro effects of factors secreted by 3 freshly explanted human colorectal-carcinoma (CRC) cell lines on lymphocyte proliferation, IL-2-receptor expression, LAK-cell generation and cytokine secretion. We found that the supernatants of all 3 CRC cell lines inhibited T-cell proliferation in a dose-dependent manner, due to the secretion of immunosuppressive factors (ISFs). In addition, the supernatants of 2 cell lines were able to inhibit LAK-cell generation and to depress IL-2R, but not HLA-DR expression, on PHA-activated T cells. Furthermore, the secretion of cytokines, i.e., IFN-gamma, IL-1beta, IL-2 and TNF-alpha, by peripheral-blood mononuclear cells (PBMC) was differently modulated by the tumor-cell supernatants, e.g., the production of IFN-gamma was reduced in normal PBMC stimulated with PHA. However, the effects induced by the supernatants were not identical: for example, factors from one CRC cell line (w25) influenced early and late events of T-cell activation and division, while 2 others (w19 and te6) contributed only to the inhibition of early events. Some biochemical properties of the ISFs were characterized. Our results suggest that colon-tumor cells can secrete ISFs, which may lead to the in vivo immunosuppression often observed in patients with these tumors.
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