TUMOR-DERIVED TRANSFORMING GROWTH-FACTOR-BETA-1 AND INTERLEUKIN-6 ARECHEMOTACTIC FOR LYMPHOKINE-ACTIVATED KILLER-CELLS

Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 a ctivated natural killer (NK) cells with potent anti-tumor cytotoxic ac tivity. They have been used in the adoptive immunotherapy of metastati c cancers. However, it has been shown that intravenously transferred L AK cells have a poor homing capacity to tumor sites. For the present s tudy, the effects of tumor-derived factors on the in vitro migratory c apacity of A-LAK cells was investigated. In a micropore migration assa y the conditioned medium from 3LL Lewis lung carcinoma cell cultures w as found to exert a strong chemotactic, but not chemokinetic effect on A-LAK cells. This effect was partially inhibited by neutralizing anti bodies against the cytokines TGF-beta I and IL-6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor- cell-conditioned medium. Purified TGF-beta I and recombinant IL-6 were chemotactic for A-LAK cells. Biological activities of both cytokines were detectable in the tumor-cell-conditioned medium. The in vivo rele vance of these findings, with respect to tissue infiltration of NK cel ls and LAK cells in inflammation or cancer, remains to be elucidated. (C) 1994 Wiley-Liss, Inc.