TY - JOUR
T1 - Interleukin-15 in cancer immunotherapy
T2 - IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model
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.
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/12/19
Y1 - 2019/12/19
N2 - 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.
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.
KW - Cancer immunotherapy
KW - Interleukin-15
KW - Leukemia
KW - NK-cells
KW - T-cells
UR - http://www.scopus.com/inward/record.url?scp=85077039263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077039263&partnerID=8YFLogxK
U2 - 10.1186/s40425-019-0777-8
DO - 10.1186/s40425-019-0777-8
M3 - Article
C2 - 31856922
AN - SCOPUS:85077039263
SN - 2051-1426
VL - 7
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 355
ER -