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IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

ABSTRACT: IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

PROVIDER: PRJNA880771 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21590411_1.fastq.gz	Fastqsanger.gz
	SRR21590411_2.fastq.gz	Fastqsanger.gz
	SRR21590412_1.fastq.gz	Fastqsanger.gz
	SRR21590412_2.fastq.gz	Fastqsanger.gz
	SRR21590413_1.fastq.gz	Fastqsanger.gz

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IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (scRNA-Seq)

Project description:Cytokines interact with their receptors in the extracellular space to control immune responses. How the physicochemical properties of the extracellular space influence cytokine signaling is incompletely elucidated. Here, we show that the activity of interleukin (IL)-2, a critical cytokine in T cell immunity, is profoundly affected by pH, limiting IL-2 signaling within the acidic environment of tumors. Generation of lactic acid by tumors limits STAT5 activation, effector differentiation and anti-tumor immunity by CD8+ T cells and renders high-dose IL-2 therapy poorly effective. Directed evolution enabled selection of a pH-selective IL-2 mutein (Switch-2). Switch-2 binds the IL-2 receptor subunit IL-2Ra with higher affinity, triggers STAT5 activation and drives CD8+ T cell effector function more potently at acidic pH than at neutral pH. Consequently, high-dose Switch-2 therapy induces potent immune activation and tumor rejection with reduced on-target toxicity in normal tissues. Finally, we find that sensitivity to pH is a generalizable property of a diverse range of cytokines with broad relevance to immunity and immunotherapy in healthy and diseased tissues.

2022-12-02 | GSE213440 | GEO

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (RNA-Seq)

2022-12-02 | GSE213439 | GEO

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (scRNA-Seq)

Project description:IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (scRNA-Seq)

| PRJNA880833 | ENA

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (RNA-Seq)

Project description:IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (RNA-Seq)

| PRJNA880834 | ENA

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-02 | GSE213441 | GEO

Identification of acidic extracellular pH-modulated genes

Project description:To investigate the genes that are modulated by acidic extracellular pH, we treated the mouse B16-BL6 cells with acidic medium and then analyzed them comprehensively by cDNA microarray.

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Project description:To investigate the function of Rfg1 in sensing acidic pH and regulating filamentation in C. albicans, we performed the global gene expression profile analysis of WT and rfg1/rfg1 mutant.We reveal that Rfg1 is an essential acidic pH sensor in C. albicans. Rfg1 regulates filamentous growth in acidic pH condition via co-regulation of Rim101-Phr1 pathway, cAMP signaling pathway,and the transcription factors Bcr1, Efg1, Flo8, and Hgc1.

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Mycobacterium tuberculosis transcriptional responses to acidic pH and carbon source

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Identification of acidic extracellular pH-modulated genes

Project description:Identification of acidic extracellular pH-modulated genes

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