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Ota Y, Ishihara S, Otani K, et al. Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes. Mol Clin Oncol. 2016;4(4):607-610doi: 10.3892/mco.2016.763.
Ota, Y., Ishihara, S., Otani, K., Yasuda, K., Nishikawa, T., Tanaka, T., Tanaka, J., Kiyomatsu, T., Kawai, K., Hata, K., Nozawa, H., Kazama, S., Yamaguchi, H., Sunami, E., Kitayama, J., & Watanabe, T. (2016). Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes. Molecular and clinical oncology, 4(4), 607-610. https://doi.org/10.3892/mco.2016.763
Ota, Yoshiko, et al. "Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes." Molecular and clinical oncology vol. 4,4 (2016): 607-610. doi: https://doi.org/10.3892/mco.2016.763
Ota Y, Ishihara S, Otani K, Yasuda K, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Hata K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T. Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes. Mol Clin Oncol. 2016 Apr;4(4):607-610. doi: 10.3892/mco.2016.763. Epub 2016 Feb 03. PMID: 27073674; PMCID: PMC4812150.
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Mol Clin Oncol. 2016 Apr;4(4):607-610. doi: 10.3892/mco.2016.763. Epub 2016 Feb 03.

Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes.

Molecular and clinical oncology

Yoshiko Ota, Soichiro Ishihara, Kensuke Otani, Koji Yasuda, Takeshi Nishikawa, Toshiaki Tanaka, Junichiro Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hiroaki Nozawa, Shinsuke Kazama, Hironori Yamaguchi, Eiji Sunami, Joji Kitayama, Toshiaki Watanabe

Affiliations

  1. Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

PMID: 27073674 PMCID: PMC4812150 DOI: 10.3892/mco.2016.763

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.

Keywords: IFN-γ; IL-4; Th2 predominance; cytokine; glucose; nutrient starvation; peripheral blood lymphocyte; proliferation

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