Faculty Research 1990 - 1999

Title

IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations.

Document Type

Article

Publication Date

1997

Keywords

Animal, Antineoplastic-Agents-Alkylating, Antineoplastic-Agents-Combined, Combined-Modality-Therapy, Cyclophosphamide, Human, Immunotherapy-Adoptive, Interleukin-15, Killer-Cells-Natural: im, cy, tr, Mice, Mice-Inbred-C57BL, Rhabdomyosarcoma: im, th, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Time-Factors

JAX Source

Cell Immunol 1997 Jul 10;179(1):66-73

Grant

CA34196/CA/NCI

Abstract

The daily administration of IL-15 to cyclophosphamide (CY)-injected mice bearing the 76-9 rhabdomyosarcoma was shown to prolong the period of 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 cell activity but there was no evidence for class I-restricted cytolytic T cell activity. To determine whether IL-15 was likely to induce different cytotoxic effectors at the tumor site compared with the spleen, tumors were removed after CY injection and cell suspensions were incubated with IL-15 in parallel with isolated spleen cells. Both populations 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 LGL-1+ cells and cells expressing early and late NK cell differentiation antigens. Both expanded populations expressed high NK cell cytotoxic activity but only the spleen cells expressed lymphocyte-activated killer cell activity. It was apparent that the expanded tumor-associated NK cells expressed low-level class I-restricted lytic activity. The potential of activated NK cells in the circulation to exert anti-tumor effects was shown by the adoptive transfer of expanded NK cells to tumor-bearing mice after CY injection when significant prolongation of life 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.

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