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Imiquimod-Loaded Phospholipid-Free Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases

ABSTRACT: Imiquimod-Loaded Phospholipid-Free Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases

PROVIDER: PRJNA1221845 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32295164_1.fastq.gz	Fastqsanger.gz
	SRR32295164_2.fastq.gz	Fastqsanger.gz
	SRR32295165_1.fastq.gz	Fastqsanger.gz
	SRR32295165_2.fastq.gz	Fastqsanger.gz
	SRR32295166_1.fastq.gz	Fastqsanger.gz

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Project description:Imiquimod is a Toll-like receptor (TLR)-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (N = 22) or vehicle cream (N=14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hrs for 4 or 8 days). RNA was amplified and hybridized to 17.5K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 X 4days regimen, associated with highest effectiveness, induced the most changes with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-Â involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. This study based on a powerful and reproducible model of cancer eradication by innate immune mechanisms provides the first insight in humans of the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction. Keywords: compound treatment design We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (N = 22) or vehicle cream (N=14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hrs for 4 or 8 days). RNA was amplified and hybridized to 17.5K cDNA arrays.

Dataset Information

Imiquimod-Loaded Phospholipid-Free Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases

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