Modulations of the effector function and cytokine production of human lymphocytes by secreted factors derived from colorectal-carcinoma cells.
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.
Luo
J S
JS
Institute of Immunobiology, University of Freiburg, Germany.
Kammerer
R
R
Schultze
H
H
von Kleist
S
S
D015179:Colorectal Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins