The molecular connections between homeostatic systems that maintain both genome integrity and proteostasis are poorly understood. Here we identify the selective activation of the unfolded protein response transducer IRE1α under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1α signaling in the absence of an endoplasmic reticulum (ER) stress signature, leading to the exclusive activation of regulated IRE1α-dependent decay (RIDD) without activating it...
Bharath et al., 2020 report that CD4+ T lymphocytes from aged individuals exhibit defective mitochondrial autophagy, resulting in altered redox metabolism and upregulation of TH17 cytokines, which in turn may contribute to aging-associated chronic inflammation or “inflammaging.” Of note, the antiaging drug metformin reverses this autophagy defect and rejuvenates CD4+ T cell function.
Nicotinamide (NAM) is a precursor of vitamin B3 commonly sold over the counter as nutritional supplement with antiaging properties. Accumulating preclinical evidence indicates that NAM also mediates oncopreventive effects against a variety of neoplasms. Supporting the translational relevance of dietary NAM supplementation, results from a Phase 3 randomized clinical trial demonstrate that oral NAM is safe and efficiently reduce the incidence of new non-melanoma skin cancers and actinic keratosis ...
The pharmacological targeting of polyamine metabolism is currently under the spotlight for its potential in the prevention and treatment of several age-associated disorders. Here, we report the finding that triethylenetetramine dihydrochloride (TETA), a copper-chelator agent that can be safely administered to patients for the long-term treatment of Wilson disease, exerts therapeutic benefits in animals challenged with hypercaloric dietary regimens. TETA reduced obesity induced by high-fat diet, ...
Autophagy is a catabolic pathway with multifaceted roles in cellular homeostasis. This process is also involved in the antiviral response at multiple levels, including the direct elimination of intruding viruses (virophagy), the presentation of viral antigens, the fitness of immune cells, and the inhibition of excessive inflammatory reactions. In line with its central role in immunity, viruses have evolved mechanisms to interfere with or to evade the autophagic process, and in some cases, even t...
#1Yi Huang(USTC: University of Science and Technology of China)H-Index: 2
#2Huanyu Wang(USTC: University of Science and Technology of China)
Last. Benjie Shan(USTC: University of Science and Technology of China)
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PTEN is a dual-specificity phosphatase that is frequently mutated in human cancer, and its deficiency in cancer has been associated with therapy resistance and poor survival. Although the intrinsic tumour-suppressor function of PTEN has been well established, evidence of its role in the tumour immune microenvironment is lacking. Here, we show that chemotherapy-induced antitumour immune responses and tumour suppression rely on myeloid-cell PTEN, which is essential for chemotherapy-induced activat...
#2Bertrand Routy(UdeM: Université de Montréal)H-Index: 13
Last. Gladys Ferrere(French Institute of Health and Medical Research)H-Index: 4
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Abstract Background The development of immune checkpoint blockade (ICB) has revolutionized the clinical outcome of renal cell carcinoma (RCC). Nevertheless, improvement of durability and prediction of responses remain unmet medical needs. While it has been recognized that antibiotics (ATBs) decrease the clinical activity of ICB across various malignancies, little is known about the direct impact of distinct intestinal nonpathogenic bacteria (commensals) on therapeutic outcomes of ICB in RCC. Obj...