Reduction of cytotoxic effector cell activity in colon 38 tumours following treatment with flavone acetic acid.

Host cells have been implicated as being involved in the antitumour effects of flavone acetic acid (FAA), an agent with selectivity towards solid tumours which is currently undergoing clinical trial. To determine whether tumour-associated host cells are affected by FAA treatment, tumour-infiltrating leukocytes (TIL) were isolated from subcutaneous Colon 38 tumours, which are known to be sensitive to FAA. 1-2 x 10(5) TIL were isolated per gram of tumour, comprising mainly small lymphocytes and macrophages. Spontaneous activity against YAC-1 and P815 tumour targets was tested in a 4 h 51Cr-release assay for lymphoid cytotoxic effector cells. High levels of activity were exhibited by TIL against both P815, which is resistant to natural killer (NK) cells, and to NK-sensitive YAC-1 cells. In contrast, splenic cell populations contained only NK cell activity. Within 1 h of intraperitoneal administration of FAA (330 mg/kg) the cytotoxic effector cell activity of the TIL population was dramatically depressed, remaining low during the time in which extensive tumour necrosis became evident. In contrast, splenic NK activity was unchanged at 1 h and elevated at 4 h. The decrease in lymphoid killer activity of the TIL population following treatment argues against the primary involvement of these effector cells in mediating the antitumour action of FAA.