Low-Protein Diet Induces IRE1 alpha-Dependent Anticancer Immunosurveillance

Rubio-Patino Camila; Bossowski Jozef P.; De Donatis Gian Marco; Mondragon Laura; Villa Elodie; Aira Lazaro E.; Chiche Johanna; Mhaidly Rana; Lebeaupin Cynthia; Marchetti Sandrine; Voutetakis Konstantinos; Chatziioannou Aristotelis; Castelli Florence A.; Lamourette Patricia; Chu-Van Emeline; Fenaille Francois; Avril Tony; Passeron Thierry; Patterson John B.; Verhoeyen Els; Bailly-Maitre Beatrice; Chevet Eric; Ricci Jean-Ehrland

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Low-Protein Diet Induces IRE1 alpha-Dependent Anticancer Immunosurveillance

机译：低蛋白质饮食诱导IS1α依赖性抗癌免疫尿失度

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Dietary restriction (DR) was shown to impact on tumor growth with very variable effects depending on the cancer type. However, how DR limits cancer progression remains largely unknown. Here, we demonstrate that feeding mice a low-protein (Low PROT) isocaloric diet but not a low-carbohydrate (Low CHO) diet reduced tumor growth in three independent mouse cancer models. Surprisingly, this effect relies on anticancer immunosurveillance, as depleting CD8(+) T cells, antigen-presenting cells (APCs), or using immunodeficient mice prevented the beneficial effect of the diet. Mechanistically, we established that a Low PROT diet induces the unfolded protein response (UPR) in tumor cells through the activation of IRE1 alpha and RIG1 signaling, thereby resulting in cytokine production and mounting an efficient anticancer immune response. Collectively, our data suggest that a Low PROT diet induces an IRE1 alpha-dependent UPR in cancer cells, enhancing a CD8-mediated T cell response against tumors.

机译：根据癌症类型，显示膳食限制（DR）对肿瘤生长的影响很大。然而，DR限制癌症进展如何仍然很大程度上是未知的。在这里，我们证明饲喂小鼠的低蛋白质（低prot）异大饮食，但不是低碳水化合物（低CHO）饮食降低了三种独立的小鼠癌症模型中的肿瘤生长。令人惊讶的是，这种效果依赖于抗癌免疫抑制，作为消耗CD8（+）T细胞，抗原呈递细胞（APC）或使用免疫缺陷小鼠阻止饮食的有益效果。机械地，我们通过激活IS1α和Rig1信号传导，我们建立了低质量饮食在肿瘤细胞中诱导展开的蛋白质反应（UPR），从而导致细胞因子产生并安装有效的抗癌免疫应答。集体，我们的数据表明，低质量饮食诱导癌细胞中的IS1α依赖性UPR，增强了针对肿瘤的CD8介导的T细胞应答。

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《Cell metabolism》 |2018年第4期|共15页
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Rubio-Patino Camila; Bossowski Jozef P.; De Donatis Gian Marco; Mondragon Laura; Villa Elodie; Aira Lazaro E.; Chiche Johanna; Mhaidly Rana; Lebeaupin Cynthia; Marchetti Sandrine; Voutetakis Konstantinos; Chatziioannou Aristotelis; Castelli Florence A.; Lamourette Patricia; Chu-Van Emeline; Fenaille Francois; Avril Tony; Passeron Thierry; Patterson John B.; Verhoeyen Els; Bailly-Maitre Beatrice; Chevet Eric; Ricci Jean-Ehrland;
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Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

NHRF Inst Biol Med Chem &

Biotechnol Athens 11635 Greece;

NHRF Inst Biol Med Chem &

Biotechnol Athens 11635 Greece;

Univ Paris Saclay SPI Lab Etud Metab Medicaments CEA INRA MetaboHUB F-91191 Gif Sur Yvette;

Univ Paris Saclay SPI Lab Etud Metab Medicaments CEA INRA MetaboHUB F-91191 Gif Sur Yvette;

Univ Paris Saclay SPI Lab Etud Metab Medicaments CEA INRA MetaboHUB F-91191 Gif Sur Yvette;

Univ Paris Saclay SPI Lab Etud Metab Medicaments CEA INRA MetaboHUB F-91191 Gif Sur Yvette;

Univ Rennes 1 Inserm U1242 Chem Oncogenesis Stress Signaling F-35042 Rennes France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Fosun Orinove Newbury Pk CA 91320 USA;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

Univ Rennes 1 Inserm U1242 Chem Oncogenesis Stress Signaling F-35042 Rennes France;

Univ Cote Azur INSERM U1065 C3M 151 Route St Antoine de Ginestiere F-06204 Nice France;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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1. Low-Protein Diet Induces IRE1 alpha-Dependent Anticancer Immunosurveillance [J] . Rubio-Patino Camila, Bossowski Jozef P., De Donatis Gian Marco, Cell metabolism . 2018,第4期

机译：低蛋白质饮食诱导IS1α依赖性抗癌免疫尿失度
2. Low-protein diet induces, whereas high-protein diet reduces hepatic FGF21 production in mice, but glucose and not amino acids up-regulate FGF21 in cultured hepatocytes [J] . The Journal of Nutritional Biochemistry . 2016,第期

机译：低蛋白质饮食诱导，而高蛋白质饮食减少小鼠的肝FGF21，但葡萄糖而不是氨基酸上调FGF21在培养的肝细胞中
3. A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPAR alpha-dependent and -independent pathways [J] . Gloerich J, van Vlies N, Jansen GA, Journal of Lipid Research . 2005,第4期

机译：富含植物醇的饮食可通过PPARα依赖性和非依赖性途径诱导小鼠脂肪酸代谢的变化
4. Effect of Low-Energy and Low-Protein Diets on Layers inRearing Period [C] . Annual^International^Meeting of the American^Society^of^Agricultural^and^Biological^Engineers . 2020

机译：低能量和低蛋白质饮食对层层的影响
5. Screening of IRE1α Ribonuclease Inhibitors from Traditional Chinese Medicine and Underlying Anticancer Mechanisms Study [D] . Xie, Jing. 2021

机译：筛选来自中药和抗癌机制研究的IRE1α核糖核酸酶抑制剂
6. Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats [O] . Lila Otani, Hiroki Nishi, Ayaka Koyama, 2020

机译：低精氨酸和低蛋白质饮食通过生长大鼠的不同机制诱导肝脂肪积累
7. Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats [O] . Lila Otani, Hiroki Nishi, Ayaka Koyama, 2020

机译：低精氨酸和低蛋白质饮食通过生长大鼠的不同机制诱导肝脂肪积累
8. Low-Protein Diet Alters Rat Behavior and Neurotransmission in Normothermic and Hyperthermic Environments [R] . Lieberman, H. R. , Yeghiayan, S. K. , Maher, T. J. 2005

机译：低蛋白质饮食改变了常温和高温环境中的大鼠行为和神经传递

Low-Protein Diet Induces IRE1 alpha-Dependent Anticancer Immunosurveillance

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