Increased antitumor effects using IL-2 with Anti-TGF-β reveals competition between mouse NK and CD8 T Cells

Maite Alvarez, Myriam N. Bouchlaka, Gail D. Sckisel, Can M. Sungur, Mingyi Chen, William J Murphy

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1709-1716
Number of pages8
JournalJournal of Immunology
Volume193
Issue number4
DOIs
StatePublished - Aug 15 2014

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ASJC Scopus subject areas

  • Immunology

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