INHIBITORY EFFECTS OF VESICLES SHED BY HUMAN BREAST-CARCINOMA CELLS ON LYMPHOCYTE H-3 THYMIDINE INCORPORATION, ARE NEUTRALIZED BY ANTI TGF-BETA ANTIBODIES

When membrane vesicles shed in vitro by 8701-BC, a human breast carcin oma cell line, are added to peripheral blood lymphocytes, a strong, do se dependent inhibition of the lymphocyte capability to incorporate H- 3-thymidine is observed. Inhibition is evident on both PhA stimulated and non stimulated lymphocytes, it is not specie-specific and occurs a fter three days of culture. Vesicles shed by the human breast carcinom a cell line MCF-7 have inhibitory effects similar to those observed wi th 8701-BC vesicles, but vesicles shed by HT-1080, a human fibrosarcom a cell line, do not inhibit, but rather stimulate H-3-thymidine incorp oration by peripheral blood lymphocytes. The inhibitory effect of vesi cles shed by human breast car cinema cells is recovered in their acid soluble components, and it is completely neutralised by anti TGF-beta 1 antibodies. These findings suggest a role for shed vesicles, in the escape of breast carcinoma cells from immunological surveillance. The immune suppressing cytokine TGF-beta, which is produced by breast carc inoma cells, could be specifically delivered to lymphocytes reacting w ith vesicles, which are HLA positive, tumour-associated antigen-rich, membrane structures.