PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation

Di, Wu; Hu, Luni; Han, Mengwei; Deng, Yichen; Zhang, Yime; Ren, Guanqun; Zhao, Xingyu; Li, Zongxian; Zhang, Yinlian; Chen, Shanwen; Li, Jun; Shi, Yanhong; Xue, Jianxin; Wang, Pengyuan; Zhong, Chao

doi:10.1038/s42255-022-00595-9

Cited by 28 publications

(19 citation statements)

References 51 publications

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“…The high level of FA can activate PPARα signaling in T cells, which, in turn, promotes FAO and OXPHOS; however, the depletion of FA in T cells hinders their proliferation and antitumor effect 198 . Likewise, the activation of PD-1 signaling inhibited the TCR and CD28-mediated PI3K/AKT/mTOR pathway to promote FAO 199 . In addition, high levels of cholesterol can enhance the number and antitumor effect of NK cells by upregulating LDLR 149 .…”

Section: Effect Of Lipid Metabolic Reprogramming On the Tmementioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.

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Section: Effect Of Lipid Metabolic Reprogramming On the Tmementioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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“…Several single‐cell studies have indicated that ILTC metabolism tends to shift towards FAO, which inhibits the release of the inflammatory regulator IL‐22, an initiating factor that increases the development of colitis following anti‐PD‐1 therapy 236 . Unexpectedly, combining metabolic modulators with ICI treatment may increase the incidence of irAEs 176 .…”

Section: Discussionmentioning

confidence: 99%

Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity

Huang,

Li,

Zhang

et al. 2024

Clinical & Translational Med

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As single‐cell RNA sequencing enables the detailed clustering of T‐cell subpopulations and facilitates the analysis of T‐cell metabolic states and metabolite dynamics, it has gained prominence as the preferred tool for understanding heterogeneous cellular metabolism. Furthermore, the synergistic or inhibitory effects of various metabolic pathways within T cells in the tumour microenvironment are coordinated, and increased activity of specific metabolic pathways generally corresponds to increased functional activity, leading to diverse T‐cell behaviours related to the effects of tumour immune cells, which shows the potential of tumour‐specific T cells to induce persistent immune responses. A holistic understanding of how metabolic heterogeneity governs the immune function of specific T‐cell subsets is key to obtaining field‐level insights into immunometabolism. Therefore, exploring the mechanisms underlying the interplay between T‐cell metabolism and immune functions will pave the way for precise immunotherapy approaches in the future, which will empower us to explore new methods for combating tumours with enhanced efficacy.

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“…[ 36 ] In another study, metabolic reprogramming during intestinal LTi cell or ILC3 activation was dependent on the regulation of the immune checkpoint PD-1. [ 37 ] ASB3 has been reported to degrade TNF-R2 via the proteasome pathway, [ 8 ] and whether there is a correlation between this and DR3 remains to be explored. Our data confirm that targeting ASB3/TRAF6 interactions largely affects the tissue repair function of ILC3s by disrupting the intestinal barrier.…”

Section: Discussionmentioning

confidence: 99%

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

Cheng,

Xu,

Sun

et al. 2023

Preprint

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BACKGROUND & AIMS: E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Our aim was to investigate the role of ASB3 in gut epithelium inflammation. METHODS: ASB3 was quantified in the lesions of IBD patients using Western blotting, qPCR and immunohistochemistry. We treated wild-type (WT) and ASB3-/- FVB-N mice and their derived colonic organoids with dextran sulfate sodium (DSS) or TNF-α as models of colitis and assessed inflammation onset, transcriptome, microbiome and ubiquitination modifications. RESULTS: ASB3-/- mice are resistant to DSS-induced colitis. IκBα phosphorylation levels and production of pro-inflammatory factors IL-1β, IL-6, and TNF-α were reduced in colonic tissues of ASB3-/- mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotic clearance of the microbiota. In addition, ASB3 specifically interacts with TRAF6 and degrades it via the proteasomal pathway. Further analysis revealed that ASB3 enhances K48-linked polyubiquitination of TRAF6 through the interaction of its SOCS box (SOCX) domain with the TRAF6 C-terminal domain. CONCLUSIONS: ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors production by disrupting the TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.

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PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation

Cited by 28 publications

References 51 publications

The role of lipid metabolic reprogramming in tumor microenvironment

The role of lipid metabolic reprogramming in tumor microenvironment

Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

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