PT  - JOURNAL ARTICLE
AU  - Berger, Alexandra
AU  - Colpitts, Sarah J.
AU  - Seabrook, Melanie S. S.
AU  - Furlonger, Caren L.
AU  - Bendix, Maura B.
AU  - Moreau, Joshua M.
AU  - McKillop, William M.
AU  - Medin, Jeffrey A.
AU  - Paige, Christopher J.
TI  - Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model
AID  - 10.1186/s40425-019-0777-8
DP  - 2019 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 355
VI  - 7
IP  - 1
4099  - http://jitc.bmj.com/content/7/1/355.short
4100  - http://jitc.bmj.com/content/7/1/355.full
SO  - J Immunother Cancer2019 Dec 01; 7
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