Heterogeneous interleukin-15 inducibilities in murine B16 melanoma and RM-1 prostate carcinoma by interferon-alpha treatment.
Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with UV-irradiated B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and NK cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Both IL-15 mRNA and IL-15 protein are highly induced in B16alpha vaccine cells. The bulk of the induced IL-15 is shown to be cell-associated, either cytoplasmic or membranous. The current study investigated the feasibility of applying the B16alpha vaccination protocol to generate a cancer vaccine against murine RM-1 prostate carcinoma. In comparison to B16alpha vaccine cells, long-term IFN-alpha-treated RM-1 cells (RM-1alpha vaccine cells) showed significant IL-15 mRNA induction but relatively low IL-15 protein up-regulation. When UV-irradiated, a 3-fold increase in intracellular IL-15 was observed in RM-1alpha vaccine cells, suggesting UV damage may have negated a possible control mechanism for IL-15 synthesis. Efficacy of in vivo vaccination of syngeneic mice with UV-irradiated RM-1alpha and B16alpha vaccine cells showed correlation between high IL-15 level and high vaccine efficacy in B16alpha cells compared to low IL-15 level and low vaccine efficacy in RM-1alpha cells. This supports the concept that the induction of IL-15 in tumor cells can be useful for creating whole-cell cancer vaccines.
Wu
Tzu G
TG
Department of Urologic Surgery, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN, USA.
Perdigão
Joana R
JR
Umhoefer
Theresa K
TK
Cao
Jade
J
Ansari
David A
DA
Albrecht
Thomas B
TB
Knutson
Eugene P
EP
Rose
William A
WA
Jorgensen
Angela J
AJ
Ryan
Lee M
LM
Abdalla
Linda E
LE
Fleischmann
William Robert
WR
D000818:Animals; D019496:Cancer Vaccines; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D014176:Protein Biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation / Q000276:immunology
D019496:Cancer Vaccines; D016898:Interferon-alpha; D019409:Interleukin-15; D012333:RNA, Messenger