title: IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer.
abstract: We are evaluating the immune enhancing activities of cytokines for their optimum utility in augmenting cellular immune responses against lung cancer. In this study, we evaluated the mechanism of antitumor responses following IL-7 administration to mice bearing established Lewis lung cancer. IL-7 decreased tumor burden with concomitant increases in the frequency of CD4 and CD8 T lymphocyte subsets, T cell activation markers CXCR3, CD69, and CD127(low), effector memory T cells, and T cell cytolytic activity against parental tumor cells. Accompanying the antitumor responses were increases in IFN-gamma, CXCL9, CXCL10, and IL-12. Individual neutralization of CD4, CD8 T lymphocytes, or the CXCR3 ligands CXCL9 and CXCL10 reversed the antitumor benefit of IL-7, indicating their importance for optimal responses in vivo. Furthermore, IL-7 decreased the tumor-induced apoptosis of T cells with subsequent decrease of the proapoptotic marker Bim. We assessed the impact of IL-7 treatment on regulatory T cells that negatively impact antitumor immune responses. IL-7 decreased regulatory T Foxp3 as well as cell suppressive activity with a reciprocal increase in SMAD7. These results indicate that IL-7 induces CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer.
authors.affiliation: Department of Medicine, University of California Los Angeles Lung Cancer Research Program, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Asa
authors.initials: A
authors.lastname: Andersson
authors.forename: Seok-Chul
authors.initials: SC
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Upendra K
authors.initials: UK
authors.lastname: Kar
authors.forename: Raj K
authors.initials: RK
authors.lastname: Batra
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Sherven
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000276:immunology; D054357:Chemokine CXCL10 / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D054367:Receptors, CXCR3 / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D015851:Interleukin-7; D054367:Receptors, CXCR3