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ABSTRACT: Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

PROVIDER: PRJNA1153928 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30467533_1.fastq.gz	Fastqsanger.gz
	SRR30467533_2.fastq.gz	Fastqsanger.gz
	SRR30467534_1.fastq.gz	Fastqsanger.gz
	SRR30467534_2.fastq.gz	Fastqsanger.gz
	SRR30467535_1.fastq.gz	Fastqsanger.gz

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Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

Project description:Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

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Stereotactic body radiotherapy is effective in modifying the tumor genome and tumor immune microenvironment in non-small cell lung cancer or lung metastatic carcinoma [RNA-seq]

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Project description:Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC) that can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated, therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy. Experimental Design: Tumor samples were obtained from patients with resectable PDAC. Radiotherapy was delivered a median of seven days prior to surgical resection, and sections were analyzed by multiplex IHC (mIHC), RNA-Seq, and T cell receptor sequencing (TCR-Seq). Results: Analysis of SBRT-treated tumor tissue indicated reduced tumor cell density and increased immunogenic cell death relative to untreated controls. Radiotherapy promoted collagen deposition, however, vasculature was unaffected and spatial analyses lacked evidence of T cell sequestration. Conversely, SBRT resulted in fewer tertiary lymphoid structures and failed to lessen or reprogram abundant immune suppressor populations. Higher percentages of PD-1+ T cells were observed following SBRT, and a subset of tumors displayed more clonal T cell repertoires. Conclusions: These findings suggest that SBRT augmentation of antitumor immunogenicity may be dampened by an overabundance of refractory immunosuppressive populations, and support the continued development of SBRT/immunotherapy combination for human PDAC.

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Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

Project description:We report the results of a randomized, open-label pilot study evaluating oral vancomycin combined with SBRT in early-stage non-small cell lung cancer. Building on prior research, vancomycin was found to enhance antitumor effects by modulating gut microbiota and boosting immune responses notably improving progression-free and overall survival (P.F.S. and O.S.). Patients treated with vancomycin (125 mg QID for 5 weeks starting one week before SBRT) showed increased expression of antigen presenation machinary in PBMCs and councurrent T-cell activation, and significant changes in gut microbiome composition and metabolite profiles, including reduced Short Chain Fatty Acids and elevated TNF-beta levels. With minimal adverse events, vancomycin appears to synergistically enhance RT-induced antitumor immunity, positioning it as a viable strategy for improving oncological outcomes. Further studies with larger cohorts are needed to confirm these results.

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