Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.
Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.
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DOI：
10.1016/j.ccell.2016.06.005
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发表时间：
2016-07-11
期刊：
影响因子：
50.3
通讯作者：
Longo VD
中科院分区：
文献类型：
--
作者：
Di Biase S;Lee C;Brandhorst S;Manes B;Buono R;Cheng CW;Cacciottolo M;Martin-Montalvo A;de Cabo R;Wei M;Morgan TE;Longo VD
基于免疫的干预措施是实现长期无癌生存的有希望的策略。禁食以前被证明可以使肿瘤对化疗敏感，同时保护正常细胞，包括造血干细胞和免疫细胞，免受其毒副作用的影响。在这里，我们发现化疗和禁食模拟饮食（FMD）的组合增加了骨髓共同淋巴祖细胞（CLP）和细胞毒性CD 8+肿瘤浸润淋巴细胞（TILs）的水平，导致乳腺癌和黑色素瘤进展的主要延迟。在乳腺肿瘤中，这种作用部分由应激反应酶血红素加氧酶-1（HO-1）的下调介导。这些数据表明，FMD-周期与化疗组合可以通过刺激造血系统和通过增强CD 8+依赖性肿瘤细胞毒性来增强T细胞依赖性靶向杀伤癌细胞。
Immune-based interventions are promising strategies to achieve long-term cancer-free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side-effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells (CLP) and cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression. In breast tumors, this effect is partially mediated by the down-regulation of the stress-responsive enzyme heme oxygenase-1 (HO-1). These data indicate that FMD-cycles combined with chemotherapy can enhance T-cell-dependent targeted killing of cancer cells both by stimulating the hematopoietic system and by enhancing CD8+-dependent tumor-cytotoxicity.