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Cell Metab. 2018 Apr 3;27(4):828-842.e7. doi: 10.1016/j.cmet.2018.02.009.

Low-Protein Diet Induces IRE1α-Dependent Anticancer Immunosurveillance.

Author information

1
Université Côte d'Azur, INSERM U1065, C3M, 151 route de St Antoine de Ginestière, BP 23194, 06204 Nice, France.
2
Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, 11635 Athens, Greece; Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
3
Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, 11635 Athens, Greece; e-NIOS Applications PC, 17671 Kallithea-Athens, Greece.
4
Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, 91191 Gif-sur-Yvette, France.
5
Inserm U1242 «Chemistry, Oncogenesis, Stress, Signaling», Université Rennes 1, 35042 Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, 35042 Rennes, France.
6
Fosun Orinove, Newbury Park, CA 91320, USA.
7
Université Côte d'Azur, INSERM U1065, C3M, 151 route de St Antoine de Ginestière, BP 23194, 06204 Nice, France. Electronic address: ricci@unice.fr.

Abstract

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 IRE1α 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 IRE1α-dependent UPR in cancer cells, enhancing a CD8-mediated T cell response against tumors.

KEYWORDS:

ER stress; IRE1α; RIG1; UPR; anti-tumor immunity; cancer; diet; dietary restriction; immunosurveillance

PMID:
29551590
DOI:
10.1016/j.cmet.2018.02.009

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