TY - JOUR
T1 - Increased antitumor effects using IL-2 with Anti-TGF-β reveals competition between mouse NK and CD8 T Cells
AU - Alvarez, Maite
AU - Bouchlaka, Myriam N.
AU - Sckisel, Gail D.
AU - Sungur, Can M.
AU - Chen, Mingyi
AU - Murphy, William J.
PY - 2014/8/15
Y1 - 2014/8/15
N2 - Because of increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL-2 with Abs to neutralize TGF-β, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater antitumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK cell progenitors, and activated CD8 T cells, resulting in the observed antitumor effects. Combination immunotherapy also was accompanied by lesser toxicities than was IL-2 therapy alone. Additionally, we observed a dual competition between NK cells and activated CD8 T cells such that, after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory antitumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK cells and CD8 T cells in response to systemic activation.
AB - Because of increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL-2 with Abs to neutralize TGF-β, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater antitumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK cell progenitors, and activated CD8 T cells, resulting in the observed antitumor effects. Combination immunotherapy also was accompanied by lesser toxicities than was IL-2 therapy alone. Additionally, we observed a dual competition between NK cells and activated CD8 T cells such that, after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory antitumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK cells and CD8 T cells in response to systemic activation.
UR - http://www.scopus.com/inward/record.url?scp=84905992207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905992207&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1400034
DO - 10.4049/jimmunol.1400034
M3 - Article
C2 - 25000978
AN - SCOPUS:84905992207
SN - 0022-1767
VL - 193
SP - 1709
EP - 1716
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -