title: Increased antitumor effects using IL-2 with anti-TGF-β reveals competition between mouse NK and CD8 T cells.
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.
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA 95817;
authors.forename: Maite
authors.initials: M
authors.lastname: Alvarez
authors.affiliation: Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV 89557;
authors.forename: Myriam N
authors.initials: MN
authors.lastname: Bouchlaka
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA 95817;
authors.forename: Gail D
authors.initials: GD
authors.lastname: Sckisel
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA 95817;
authors.forename: Can M
authors.initials: CM
authors.lastname: Sungur
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817; and.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA 95817; Department of Internal Medicine, University of California, Davis, Sacramento, CA 95817 wmjmurphy@ucdavis.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000096:biosynthesis; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis; D009369:Neoplasms / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D019014:fas Receptor / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; C527095:Klra7 protein, mouse; C527086:Klrk1 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016212:Transforming Growth Factor beta; D019014:fas Receptor