Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response.
Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response.
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DOI：
10.1016/j.isci.2023.107839
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发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Rattan, Ramandeep
中科院分区：
文献类型：
--
作者：
Udumula, Mary Priyanka;Singh, Harshit;Rashid, Faraz;Poisson, Laila;Tiwari, Nivedita;Dimitrova, Irina;Hijaz, Miriana;Gogoi, Radhika;Swenor, Margaret;Munkarah, Adnan;Giri, Shailendra;Rattan, Ramandeep
在各种癌症模型中，饮食干预已被证明可以抑制肿瘤生长，提高抗癌药物疗效，增强免疫力，但对于上皮性卵巢癌（EOC），最致命的妇科癌症，没有这样的证据。研究了16小时间歇性禁食（IF）诱导的卵巢癌小鼠的抗癌免疫应答。IF持续减少刺激肿瘤生长的代谢生长因子和细胞因子，创造了一个肿瘤敌对的环境。免疫分析表明，IF通过增加CD 4+和CD 8+细胞，Th 1和细胞毒性反应以及代谢适应性显著改变抗癌免疫。β-羟基丁酸酯（BHB）是IF产生的生物活性代谢物，通过诱导CD 8+效应子功能部分模仿IF的抗癌作用。在直接比较中，IF在存活率和抗肿瘤免疫应答方面优于外源性BHB治疗，这可能是由于生酮增加。因此，IF及其代谢介质之一BHB抑制EOC生长并维持有效的抗肿瘤T细胞应答。在EOC中，IF增加存活率并增强T细胞介导的免疫应答IF介导的保护作用在T细胞缺乏的情况下被消除IF导致BHB的丰富，这概括了IF的抗肿瘤作用IF比外源性BHB治疗更能提高存活率生物科学;生理学;免疫学;癌症
In various cancer models, dietary interventions have been shown to inhibit tumor growth, improve anticancer drug efficacy, and enhance immunity, but no such evidence exists for epithelial ovarian cancer (EOC), the most lethal gynecologic cancer. The anticancer immune responses induced by 16-h intermittent fasting (IF) were studied in mice with EOC. IF consistently reduced metabolic growth factors and cytokines that stimulate tumor growth, creating a tumor-hostile environment. Immune profiling showed that IF dramatically alters anti-cancer immunity by increasing CD4+ and CD8+ cells, Th1 and cytotoxic responses, and metabolic fitness. β-hydroxy butyrate (BHB), a bioactive metabolite produced by IF, partially imitates its anticancer effects by inducing CD8+ effector function. In a direct comparison, IF outperformed exogenous BHB treatment in survival and anti-tumor immune response, probably due to increased ketogenesis. Thus, IF and one of its metabolic mediators BHB suppress EOC growth and sustain a potent anti-tumor T cell response. IF increases survival and potentiates T cell-mediated immune responses in EOC IF-mediated protective effects were abolished in the absence of T cells IF resulted in abundance of BHB, which recapitulated the anti-tumor effects of IF IF improved survival more than exogenous BHB therapy Biological sciences; Physiology; Immunology; Cancer
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DOI：
10.1080/01635581.2019.1645864
发表时间：
2019-07-26
影响因子：
2.9
作者：
Cohen, Caroline W.;Fontaine, Kevin R.;Gower, Barbara A.
通讯作者：
Gower, Barbara A.
影响因子：
11.1
作者：
Hirschberger S;Strauß G;Effinger D;Marstaller X;Ferstl A;Müller MB;Wu T;Hübner M;Rahmel T;Mascolo H;Exner N;Heß J;Kreth FW;Unger K;Kreth S
通讯作者：
Kreth S
DOI：
10.1016/j.tem.2018.01.008
发表时间：
2018-04
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Buono R;Longo VD
通讯作者：
Longo VD
影响因子：
4.6
作者：
Dar S;Chhina J;Mert I;Chitale D;Buekers T;Kaur H;Giri S;Munkarah A;Rattan R
通讯作者：
Rattan R
影响因子：
64.5
作者：
Ho PC;Bihuniak JD;Macintyre AN;Staron M;Liu X;Amezquita R;Tsui YC;Cui G;Micevic G;Perales JC;Kleinstein SH;Abel ED;Insogna KL;Feske S;Locasale JW;Bosenberg MW;Rathmell JC;Kaech SM
通讯作者：
Kaech SM