IL-15 MEDIATES ANTITUMOR EFFECTS AFTER CYCLOPHOSPHAMIDE INJECTION OF TUMOR-BEARING MICE AND ENHANCES ADOPTIVE IMMUNOTHERAPY - THE POTENTIALROLE OF NK CELL SUBPOPULATIONS
R. Evans et al., IL-15 MEDIATES ANTITUMOR EFFECTS AFTER CYCLOPHOSPHAMIDE INJECTION OF TUMOR-BEARING MICE AND ENHANCES ADOPTIVE IMMUNOTHERAPY - THE POTENTIALROLE OF NK CELL SUBPOPULATIONS, Cellular immunology, 179(1), 1997, pp. 66-73
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.