Project description:Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.
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
Project description:To characterize the primary and recall responses to EV71 vaccines, PBMCs from 19 recipients before and after vaccination with EV71 vaccine were collected. 14 samples pre-vaccination and 16 samples post-vaccination were detected by microarray and their gene expression signatures after stimulation with EV71 antigen were compared.
Project description:To characterize the primary and recall responses to EV71 vaccines, PBMC from 19 recipients before and after vaccination with EV71 vaccine are collected and their gene expression signatures after stimulation with EV71 antigen were compared. Four-condition experiment,pre-vaccination PBMCs (stimulation vs. no stimulation with EV71 antigen) vs. post-vaccination PBMCs (stimulation vs. no stimulation with EV71 antigen)
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).
Project description:To elucidate the epithelial cell diversity within the nasal inferior turbinates, a comprehensive investigation was conducted comparing control subjects to individuals with house dust mite-induced allergic rhinitis. This study aimed to delineate the differential expression profiles and phenotypic variations of epithelial cells in response to allergic rhinitis. This research elucidated distinct subpopulations and rare cell types of epithelial cells within the nasal turbinates, discerning alterations induced by allergic rhinitis. Furthermore, by interrogating transcriptomic signatures, the investigation provided novel insights into the cellular dynamics and immune responses underlying allergic rhinitis pathogenesis
