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Hysteresis of IL-10R primes solid tumour microenvironment for bacterial immunotherapy

ABSTRACT: Hysteresis of IL-10R primes solid tumour microenvironment for bacterial immunotherapy

PROVIDER: PRJNA1095870 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28539136.fastq.gz	Fastqsanger.gz
	SRR28539137.fastq.gz	Fastqsanger.gz
	SRR28539138.fastq.gz	Fastqsanger.gz
	SRR28539139.fastq.gz	Fastqsanger.gz

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Hysteresis of IL-10R primes solid tumour microenvironment for bacterial immunotherapy

Project description:Hysteresis, a ubiquitous phenomenon in nonlinear systems, plays a vital role in diverse scientific disciplines. Here, we demonstrated the presence of hysteresis in the expression of interleukin-10 receptor (IL-10R) within the tumour microenvironment (TME) during bacterial immunotherapy. The engineered Salmonella enterica, administered intravenously, exhibited remarkable efficacy in multiple tumour types, effectively eliminating tumours and preventing recurrence and metastasis. We found that the hysteretic response of IL-10R can prime TME for bacterial homing and reinvigorate intratumoural CD8+ T cells. Furthermore, the differential IL-10R levels observed in different human tumour types suggest a potential correlation with clinical outcomes. Overall, our study not only uncovers the central role of hysteresis in driving the therapeutic effects of bacterial immunotherapy, but also provides a framework for intratumoural immunomodulation in solid tumour treatment.

2024-04-10 | GSE263108 | GEO

Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [ATACseq]

Project description:Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [ATACseq]

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Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [ATACseq]

Project description:Bacterial immunotherapy holds promising cancer-fighting potential. However, unlocking its power requires a mechanistic understanding of how bacteria both evade antimicrobial immune defenses and stimulate antitumor immune responses within the tumor microenvironment (TME). Here, by harnessing an engineered Salmonella enterica strain with this dual proficiency, we unveiled a singular mechanism underlying. Specifically, the hysteretic nonlinearity of interleukin-10 receptor (IL-10R) expression drives tumor-infiltrated immune cells into a tumor-specific IL-10Rhi state. Bacteria leverage this to enhance tumor-associated macrophages producing IL-10, evade phagocytosis by tumor-associated neutrophils, and coincidently expand and stimulate the preexisting exhausted tumor-resident CD8+ T cells. This effective combination eliminated tumors, prevented recurrence, and inhibited metastasis across multiple tumor types. Analysis of human samples suggested that IL-10Rhi state might be a ubiquitous trait across human tumor types. Our study unveils the unsolved mechanism behind bacterial immunotherapy's dual challenge in solid tumors and provides a framework for intratumor immunomodulation.

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Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [RNA-Seq]

Project description:Bacterial immunotherapy leveraging IL-10R hysteresis for both phagocytosis evasion and tumor immunity revitalization [RNA-Seq]

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