title: Requirement of interleukin 7 signaling for anti-tumor immune response under lymphopenic conditions in a murine lung carcinoma model.
abstract: Induction of lymphopenia before adoptive transfer of T cells was followed by lymphopenia-induced proliferation (LIP) and generated a potent anti-tumor immune response in rodents and in a clinical setting. Previously, we reported that CD28 signaling is essential for the differentiation of functional effector cytotoxic T lymphocytes (CTLs) under lymphopenic conditions and sequential LIP of T cells. In this study, to clarify the correlation between LIP and the anti-tumor effect, LIP was inhibited with interleukin 7 (IL7) receptor blockade at various stages, and the anti-tumor effect then assessed. We confirmed that IL7 signaling at the start of LIP is crucial for the anti-tumor immune response. In contrast, continuous IL7 signaling was not required for tumor regression, although LIP of naïve CD8+ T cells is usually regulated by IL7. The expansion and migration of CTLs in lymphopenic hosts depend on IL7 signaling during the induction phase. Here, we propose that IL7 signaling and subsequent LIP of T cells have distinct roles in the induction of T cell immunity during lymphopenia.
authors.affiliation: Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Parasitology and Immunopathoetiology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan. rabe@rs.noda.tus.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015851:Interleukin-7 / Q000502:physiology*; D037181:Lectins, C-Type; D008175:Lung Neoplasms / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis; D020395:Receptors, Interleukin-7 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015851:Interleukin-7; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7
keywords: Anti-tumor immune response; CD28; Interleukin 7; Lymphopenia-induced proliferation; Priming and induction of CTLs