RT Journal Article
SR Electronic
T1 Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 355
DO 10.1186/s40425-019-0777-8
VO 7
IS 1
A1 Berger, Alexandra
A1 Colpitts, Sarah J.
A1 Seabrook, Melanie S. S.
A1 Furlonger, Caren L.
A1 Bendix, Maura B.
A1 Moreau, Joshua M.
A1 McKillop, William M.
A1 Medin, Jeffrey A.
A1 Paige, Christopher J.
YR 2019
UL http://jitc.bmj.com/content/7/1/355.abstract
AB Cytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed with IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms of IL-15 led to significantly improved survival rates compared to the parent cell line, there were striking differences in the extent of the improved survival: mice receiving cancer cells secreting IL-15sol showed significantly longer survival and protective long-term immunity compared to those producing IL-15Rc. Interestingly, injection of leukemia cells secreting IL-15sol lead to heightened expansion of CD4+ and CD8+ T-cell populations in the peritoneum compared to IL-15Rc. Cell-secreted IL-15Rc resulted in an influx and/or expansion of NK1.1+ cells in the peritoneum which was much less pronounced in the IL-15sol model. Furthermore, IL-15Rc but not IL-15sol lead to T-cell exhaustion and disease progression. To our knowledge, this is the first study detailing a significantly different biological effect of cell-delivered IL-15sol versus IL-15Rc in a mouse cancer immunotherapy study.Abbreviations:FCSFetal calf serumG-CSFGranulocyte-colony stimulating factorGFPGreen fluorescent proteinGM-CSFGranulocyte-macrophage colony-stimulating factorGrzBGranzyme B; hr., hourIFN-γInterferon-γIL-15RcIL-15 receptor complexIL-15solSoluble IL-15ipIntra-peritonealIP-10IFN-γ-inducible protein 10KCChemokine ligand 1 (CXCL1)LVLentivirusMCP-1Monocyte chemoattractant protein-1MIGMonokine induced by IFN-γ (CXCL9)NK-cellNatural killer cellONOver nightPBSPhosphate buffered salinevsVersus