Tumor-derived transforming growth factor-β1 and interleukin-6 are chemotactic for lymphokine-activated killer cells
✍ Scribed by Nadia Delens; Els Torreele; Huub Savelkool; Patrick de Baetselier; Luc Bouwens
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 599 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Adherent lymphokine-activated killer (A-LAK) cells are purified IL-2 activated natural killer (NK) cells with potent antitumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic cancers. However, it has been shown that intravenously transferred IAK cells have a poor homing capacity to tumor sites. For the present study, the effects of tumor-derived factors on the in vitro migratory capacity of A-LAK cells was investigated. In a micropore migration assay the conditioned medium from 3LL Lewis lung carcinoma cell cultures was found to exert a strong chemotactic, but not chemokinetic effect on A-LAK cells. This effect was partially inhibited by neutralizing antibodies against the cytokines TGF-PI and IL-6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor-cellconditioned medium. Purified TGF-P 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 relevance of these findings, with respect to tissue infiltration of NK cells and LAK cells in inflammation or cancer, remains to be elucidated. o I994 Wiley-Liss, Inc.
LAK cells are large granular lymphocytes generated by the culture of normal lymphocytes with IL-2. This procedure provides cells with a broad anti-tumor reactivity, which has already been used in anticancer therapy . The nature of LAK cells is controversial, but it is generally accepted that most of the cytotoxicity is mediated by activated NK cells . These activated NK cells can be generated in large numbers and with a high purity by selection according to plastic adherence .