IL-15 MEDIATES ANTITUMOR EFFECTS AFTER CYCLOPHOSPHAMIDE INJECTION OF TUMOR-BEARING MICE AND ENHANCES ADOPTIVE IMMUNOTHERAPY - THE POTENTIALROLE OF NK CELL SUBPOPULATIONS

The daily administration of IL-15 to cyclophosphamide (CY)-injected mi ce bearing the 76-9 rhabdomyosarcoma was shown to prolong the period o f remission induced by CY. In addition, IL-15 was shown to enhance the efficacy of adoptive immunotherapy. Cytotoxicity assays using spleens from normal and tumor-bearing mice indicated that IL-15 enhanced NK c ell activity but there was no evidence for class I-restricted cytolyti c T cell activity. To determine whether IL-15 was likely to induce dif ferent cytotoxic effecters at the tumor site compared with the spleen, tumors were removed after CY injection and cell suspensions were incu bated with IL-15 in parallel with isolated spleen cells. Both populati ons were seen to expand to yield predominantly cells coexpressing NK1. 1 and B220 antigens. However, tumor-associated NK cells were shown to differ from expanded spleen NK cells in terms of the proportions of LG L-1(+) cells and cells expressing early and late NK cell differentiati on antigens. Both expanded populations expressed high NK cell cytotoxi c activity but only the spleen cells expressed lymphocyte-activated ki ller cell activity. It was apparent that the expanded tumor-associated NK cells expressed low-level class I-restricted lytic activity. The p otential of activated NK cells in the circulation to exert anti-tumor effects was shown by the adoptive transfer of expanded NK cells to tum or-bearing mice after CY injection when significant prolongation of li fe was seen in all cases. The data indicate that IL-15 may serve as a useful anti-cancer adjuvant by activating initially the NK cell arm of the immune network. (C) 1997 Academic Press.