Inhibitory effects of vesicles shed by human breast carcinoma cells on lymphocyte 3H-thymidine incorporation, are neutralised by anti TGF-beta antibodies.

When membrane vesicles shed in vitro by 8701-BC, a human breast carcinoma cell line, are added to peripheral blood lymphocytes, a strong, dose dependent inhibition of the lymphocyte capability to incorporate 3H-thymidine is observed. Inhibition is evident on both PhA stimulated and non stimulated lymphocytes, it is not specie-specific and occurs after three days of culture. Vesicles shed by the human breast carcinoma cell line MCF-7 have inhibitory effects similar to those observed with 8701-BC vesicles, but vesicles shed by HT-1080, a human fibrosarcoma cell line, do not inhibit, but rather stimulate 3H-thymidine incorporation by peripheral blood lymphocytes. The inhibitory effect of vesicles shed by human breast carcinoma 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 carcinoma cells, could be specifically delivered to lymphocytes reacting with vesicles, which are HLA positive, tumour-associated antigen-rich, membrane structures.