title: Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes.
abstract: Proliferating cancer cells are exposed to nutrient deprivation. Numerous previous studies have demonstrated how nutrient deprivation affects cancer cells; however, immune cells exposed to the identical conditions have not been completely examined. Furthermore, T-helper 2 lymphocyte predominance in certain neoplastic diseases has been reported; however, the mechanism remains unclear. The present study aimed to confirm whether nutrient deprivation affected proliferation and cytokine secretion of peripheral blood lymphocytes (PBLs). The proliferation of PBLs from healthy donors, cultured in a medium containing various glucose levels, was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. The expression levels of interleukin (IL)-4 and interferon (IFN)-γ among CD4(+) T cells, cultured with or without glucose and activated with phorbol 12-myristate 13-acetate and ionomycin, were examined using an intracellular cytokine staining method. The proliferation of PBLs cultured in a medium containing <100 mg/dl glucose of the standard blood sugar (BS) level was significantly reduced compared with the proliferation observed in a medium containing a standard BS level or higher. PBLs cultured in a glucose-free medium contained a significantly higher percentage of IL-4-positive and a lower percentage of IFN-γ-positive CD4(+) T cells compared with those cultured in a high-glucose medium. Nutrient deprivation suppressed the proliferation of PBLs, fostered the secretion of IL-4 and reduced secretion of IFN-γ. It is therefore possible that glucose-deficient microenvironments in local cancer tissues cause a partial immunodeficiency, which is advantageous to cancer growth.
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ishihara
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Kiyomatsu
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nozawa
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kazama
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sunami
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.affiliation: Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
keywords: IFN-γ; IL-4; Th2 predominance; cytokine; glucose; nutrient starvation; peripheral blood lymphocyte; proliferation