Imiquimod-Loaded Phospholipid-Free Unilamellar Vesicles Activate the Tumor Immune Microenvironment to Treat Liver Cancer and Liver Metastases
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PROVIDER: PRJNA1221845 | ENA |
REPOSITORIES: ENA
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Project description:Liver cancers are often diagnosed at advanced stages and the fourth most common cause of cancer death globally. Addition to primary tumours, liver metastases are also common from other cancer sites like colorectal cancers, where 66% of patients develop this condition. Immunotherapies for these diseases have been hindered by the immunosuppressive microenvironment. Our lab has developed phospholipid-free unilamellar vesicles (PFSUV) to localize a toll-like receptor 7 agonist Imiquimod (IMQ), to the hepatocytes. PFSUV is composed of 83 mol% cholesterol and 17 mol% Tween80 and IMQ was loaded inside the aqueous core of these 75-nm particles. When administered intravenously (i.v.), PFSUV-IMQ was found to sustain IFN-α levels in the liver over 24 hours, with significantly lower plasma IFN-α levels compared to free IMQ. In a mouse model of liver metastasis from a colorectal cancer origin generated with CT26 cells, mice treated with PFSUV-IMQ in combination with Oxaliplatin showed a significant reduction in tumour size, with increases in CD8+ T cell and a higher percentage of apoptotic cells in the tumour compared to controls. In a mouse model of primary liver cancer using HCA-1 cells, the same treatment combination also showed a significant decrease in tumour burden, increased apoptotic cell percentage in the tumour, and significantly reduced lung metastasis from the liver compared to controls. Flow cytometry analysis showed tumours treated with PFSUV-IMQ had increased infiltration of CD86+/MHC-II+ dendritic cells and IFN-y+ CD8+ T cells. RNA-seq showed an enrichment of innate immune activation genes after a single dose of PFSUV-IMQ. Overall, these data suggest that the activation of the tumour immune microenvironment through this targeted delivery of IMQ resulted in a decrease in tumour burden across both liver tumour models.
2025-03-01 | GSE289163 | GEO
Project description:The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days). RNA was extracted from 4 spontaneous tumors from neu-tg mice treated with topical imiquimod for 1 cycle and 4 spontaneous tumors from control mice
2010-06-24 | E-GEOD-20032 | biostudies-arrayexpress
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.
2006-10-04 | E-GEOD-5121 | biostudies-arrayexpress
Project description:The imiquimod model is used to induce the skin production of IL-22 and to characterize the cells that produce IL-22 in the skin after inflammatory stimulus. This experiment is performed on skin of C57Bl/6 mice treated with imiquimod to induce psoriasis-like lesions. After 5 days of imiquimod treatment, we analysed the heamatopoietic cells that infiltrate the skin and we compared the gene signature of three T cell populations: CD4+ T cells, CD4-CD8-(DN) T cells and gd T cells
2016-08-09 | E-MTAB-4453 | biostudies-arrayexpress
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2023-12-25 | GSE223871 | GEO
Project description:The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days).
2010-01-26 | GSE20032 | GEO
Project description:Farmed and wild Atlantic salmon was given either vegetable oil (low DHA and EPA) feed or fish oil (high in DHA and EPA) feed or phospholipid (high in phospholipid) feed from start of feeding. We sampled and RNAseq two tissues (pyloric caeca and liver) on day 0, day 48, day 65 and day 94 after initial feeding.
2019-10-30 | E-MTAB-8306 | biostudies-arrayexpress
Project description:Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high fat/high cholesterol/high sucrose/bile salt diet (NASH diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5±9.8 vs. 83.1±13.1 pg/ml, p<0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14±0.75 vs. 5.17±1.17, p<0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.
2022-12-27 | GSE214836 | GEO
Project description:We provide a new psoriasis mouse model which is induced by p38 activation in skin. We compared the individual transcriptomic profiles of anisomycin and imiquimod-induced dermatitis. We used microarrays to compare the gene expression pattern between anisomycin- and imiquimod- induced dermatitis.
2019-02-15 | GSE110658 | GEO
Project description:pH-Degradable, Bisphosphonate-Loaded Nanogels Repolarize Immunosuppressive Macrophages Towards Antifibrotic Liver Therapy
| PRJNA771672 | ENA