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RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumor immunity

ABSTRACT: RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumor immunity

PROVIDER: PRJNA957281 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24210806_1.fastq.gz	Fastqsanger.gz
	SRR24210806_2.fastq.gz	Fastqsanger.gz
	SRR24210807_1.fastq.gz	Fastqsanger.gz
	SRR24210807_2.fastq.gz	Fastqsanger.gz
	SRR24210808_1.fastq.gz	Fastqsanger.gz

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RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumor immunity

Project description:RIG-I is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity remains unclear. Here, we demonstrate that RIG-I is upregulated in tumor infiltrating CD8+ T cells, where it functions as an intracellular checkpoint to negatively regulate CD8+ T cell function and limit antitumor immunity. Mechanically, up-regulation of RIG-I in CD8+ T cells is induced by retinoic acid (RA), a metabolite of vitamin A in TME, and direct inhibits the AKT/glycolysis signaling pathway. In addition, deletion of RIG-I enhances the efficacy of adoptively transferred T cells against solid tumors and inhibition of RIG-I enhances the response to PD-1 blockade. Our findings identify RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with immune checkpoint blockade.

2023-04-25 | GSE230045 | GEO

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Project description:RIG-I is an intracellular checkpoint that limits CD8+ T-cell antitumor immunity

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UBE2D3 is an Intracellular Checkpoint in Pancreatic Ductal Carcinoma that Restricts CD8+ T-Cell Antitumor Immunity

Project description:UBE2D3 is an Intracellular Checkpoint in Pancreatic Ductal Carcinoma that Restricts CD8+ T-Cell Antitumor Immunity

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UBE2D3 is an Intracellular Checkpoint in Pancreatic Ductal Carcinoma that Restricts CD8+ T-Cell Antitumor Immunity II

Project description:UBE2D3 is an Intracellular Checkpoint in Pancreatic Ductal Carcinoma that Restricts CD8+ T-Cell Antitumor Immunity II

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RIG-I is an intracellular checkpoint that limits CD8<sup>+</sup> T-cell antitumour immunity.

Project description: Not available

| S-EPMC11555380 | biostudies-literature

Asparagine regulates RIG-I stability to suppress anti-tumor immunity in bladder cancer

Project description:Tumor cells often employ many ways to restrain type I interferon (IFN-I) signaling to evade immune surveillance. However, whether cellular amino acid metabolism regulate this process remains unclear and its effects on antitumor immunity are relatively unexplored. Here, our study reports that asparagine generated by asparagine synthetase (ASNS) inhibits IFN-I signaling and promotes immune escape in bladder cancer. We further show that depletion of ASNS strongly limits in vivo tumor growth in a CD8+ T cell-dependent manner, thus boosting the immunotherapy efficacy. Moreover, clinically approved ASNase synergizes with anti-PD-1 therapy in suppressing tumor growth in mouse models of bladder cancer. Mechanistically, asparagine intensifies the interaction of E3 ligase CBL and RIG-I, promoting K48-linked polyubiquitination and degradation of RIG-I, thus suppressing RIG-I mediated IFN signaling and anti-tumor immune response. Clinically, ASNS is overexpressed in muscle-invasive bladder cancer and correlated with poor response of immunotherapy. Together, our findings uncover asparagine as a natural metabolite to modulate RIG-I-mediated IFN-I signaling, providing the basis for developing the combinatorial use of ASNase and anti-PD-1 for bladder cancer.

2025-03-19 | GSE270353 | GEO

STUB1 is an intracellular checkpoint for interferon gamma sensing

Project description:STUB1 is an intracellular checkpoint for interferon gamma sensing

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An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

Project description:An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

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An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

Project description:An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

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An intracellular magnetic torque-regulator drives mechano-sequential antitumor immunity

Project description:Nature creates specific structures to control mechanical plasticity for cell fate regulation. Although immune cells can sense and adapt to extracellular mechanical cues, how to activate immune responses via intracellular mechanical stimulation remains a mystery. Here, we present an intelligent intracellular magnetic torque (IIMT) paradigm that is coupled with programmed rotating magnetic fields to generate the selective mechano-stimulations in lysosomes and induce sequential antitumor immune responses. A magnetic rod-shaped micromotor (MagRM) with the a unique geometric aspect ratio is designed to exert tunable torques in antigen-presenting cells (APCs) and tumor cells. Low-intensity torque induces the mild lysosomal membrane damage to trigger antigen cross-presentation and canonical NLRP3 inflammasome activation in APCs, whereas high-intensity torque causes lysosomal membrane rupture for immunogenic cell death. In vivo studies unveil that the optimal antitumor activity is achieved by generating sequential torques from high to low intensities, which is illuminating to explore mechano-immunotherapy with selective and spatiotemporal control.

2025-10-15 | GSE276125 | GEO

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