Ota Yoshiko, Ishihara Soichiro, Otani Kensuke, Yasuda Koji, Nishikawa Takeshi, Tanaka Toshiaki, Tanaka Junichiro, Kiyomatsu Tomomichi, Kawai Kazushige, Hata Keisuke, Nozawa Hiroaki, Kazama Shinsuke, Yamaguchi Hironori, Sunami Eiji, Kitayama Joji, Watanabe Toshiaki
Department of Surgical Oncology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
Mol Clin Oncol. 2016 Apr;4(4):607-610. doi: 10.3892/mco.2016.763. Epub 2016 Feb 3.
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.
增殖的癌细胞会面临营养剥夺。此前众多研究已证实营养剥夺对癌细胞的影响；然而，处于相同条件下的免疫细胞尚未得到充分研究。此外，已有报道称在某些肿瘤性疾病中辅助性T细胞2占优势；然而，其机制仍不清楚。本研究旨在确认营养剥夺是否会影响外周血淋巴细胞（PBL）的增殖和细胞因子分泌。通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑鎓内盐（MTS）试验评估来自健康供体的PBL在含有不同葡萄糖水平的培养基中培养时的增殖情况。使用细胞内细胞因子染色方法检测在有或无葡萄糖培养并用佛波醇12-肉豆蔻酸酯13-乙酸酯和离子霉素激活的CD4(+) T细胞中白细胞介素（IL）-4和干扰素（IFN）-γ的表达水平。与在含有标准血糖（BS）水平或更高水平的培养基中观察到的增殖相比，在含有低于标准BS水平100 mg/dl葡萄糖的培养基中培养的PBL的增殖显著降低。与在高葡萄糖培养基中培养的PBL相比，在无葡萄糖培养基中培养的PBL含有显著更高百分比的IL-4阳性和更低百分比的IFN-γ阳性CD4(+) T细胞。营养剥夺抑制了PBL的增殖，促进了IL-4的分泌并减少了IFN-γ的分泌。因此，局部癌组织中缺乏葡萄糖的微环境可能会导致部分免疫缺陷，这对癌症生长有利。
