Functional characteristics of bone marrow immune suppressive cells in patients with gastric cancer

The progressive growth of cancer is accompanied by alteration in the regulation of both hematopoiesis and immunity. In this study we assessed the immunoregulatory features of bone marrow (BM) plastic nonadherent cells in patients with primary gastric cancer, Suppressive activity of BM cells or its culture supernatants was determined by inhibition of normal peripheral blood mononuclear cells (PBMC) response to phytohemagglutinin (PHA) or NK cell cytotoxicity, It was shown that fresh isolated BM cells from gastric cancer patients are capable markedly inhibit the mitogen-induced proliferative response of PBMC as well as NK cell cytotoxic activity. The immune suppressive cell activity was revealed among the non-adherent cell fraction only. The addition of indomethacin, inhibitor of prostaglandin synthesis, or N-G-monomethyl-L-arginine (L-NMA), a competitive inhibitor of nitric oxide (NO) synthase, to the cultures did not diminish the suppressive effect of non-adherent BM cells in cancer patients. This BM cell mediated suppression of mitogen-induced proliferation of PBMC could be reduced, at least in part, by addition of neutralizing monoclonal antibodies to TGF-beta. When normal PBMC were cultured with supernatant of BM cells derived from cancer patients, their natural killer cell activity was strongly down-regulated. It was shown also that NK cell capacity to bind tumor target cells was reduced in the presence of BM cell supernatant, Taken together our data demonstrate that BM non-adherent cell of patients with gastric cancer exhibit the immune suppressive activity which should be supposed to contribute to impairment of tumor immunity as malignant growth progresses.