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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Mammary Fat Pad RNA-seq]

ABSTRACT: Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Mammary Fat Pad RNA-seq]

PROVIDER: PRJNA731484 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14605841_1.fastq.gz	Fastqsanger.gz
	SRR14605841_2.fastq.gz	Fastqsanger.gz
	SRR14605842_1.fastq.gz	Fastqsanger.gz
	SRR14605842_2.fastq.gz	Fastqsanger.gz
	SRR14605843_1.fastq.gz	Fastqsanger.gz

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Mammary Fat Pad RNA-seq]

Project description:Patients undergoing bariatric surgery are protected from subsequent breast cancer risk. It is unknown whether weight loss alone or surgery-specific alterations mediate risk reduction. We examined breast cancer in a pre-clinical model of diet induced obesity (DIO) followed by vertical sleeve gastrectomy (VSG) or dietary weight loss. DIO exacerbated tumor progression compared to lean controls, while VSG-induced weight loss reversed this exacerbation. However, dietary interventions were more effective than VSG despite similar reductions in weight and adiposity, potentially due to elevated immunosuppression after VSG. In tumor bearing mice, anti-PD-L1 immunotherapy after VSG improved anti-tumor immunity and potently impaired tumor progression. Thus, weight loss before tumor onset was protective regardless of intervention. Importantly, immunotherapy specifically improved outcomes in VSG.

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy

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The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

Project description:Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is through the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant. Cecal contents were isolated from either obese controls that received sham surgery or formerly obese mice following bariatric surgery-induced weight loss and transferred by FMT to lean recipients. Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric-surgery treated mice. Microbes can impact tumor burden through microbially derived metabolites produced or modified by gut microbiota including branched chain amino acids (BCAA). Circulating BCAA correlated significantly with NK T cell content in the tumor microenvironment in both donor mice after bariatric surgery and in FMT recipients of donor cecal content after bariatric surgery compared to obese sham controls. Findings implicate a role of microbially-derived BCAA in activating anti-tumor immunity that is dependent upon bariatric surgery. Importantly, when stool from a patient who exhibited 25% weight loss post-bariatric surgery was transplanted into recipient mice and compared to the patient’s pre-bariatric surgery stool transplant. Patient samples post bariatric surgery significantly reduced tumor burden by 2.4-fold and immunotherapy effectiveness was doubled. Taken together, findings suggest that reinvigorating anti-tumor immunity may be dependent upon microbially derived metabolites such as BCAA.

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Project description:A prospective, multicenter, cohort study was conducted in patients with severe obesity, who were randomized between two bariatric surgery techniques (Roux-en-Y gastric bypass and one anastomosis gastric bypass). Fecal samples were collected from 45 obese patients before surgery (T0) and 24 months after surgery (T1) and analyzed by shotgun metaproteomics.

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Tumor - breast cancer RNA-seq]

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy

Project description:This SuperSeries is composed of the SubSeries listed below. -GEO GSE174760 (bulk mammary fat pad RNA), GSE174761 (bulk tumor RNA),

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