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Targeted regulation of cytokines expression with a portable smart light-controllable device for tumor immunotherapy

ABSTRACT: As the first type of tumor immunotherapy drugs, cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, the application of cytokines for tumor immunotherapy was still limited to their short half-time, narrow therapeutic window, and undesired side effects. Here, we constructed a portable smart light-controllable (PSLC) device to address this issue. By combining the PSLC device and light-switchable gene modules, it is theoretically possible to regulate the cytokines expressed within target tumors by optical remote control. Then, cytokine interferon-γ (IFN-γ) and chemokine CXCL10, two essential immune regulatory molecules that play crucial roles in immunotherapy, are selected to test this system.

ORGANISM(S): Mus musculus

PROVIDER: GSE214760 | GEO | 2022/10/07

REPOSITORIES: GEO

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Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.

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Targeted regulation of cytokines expression with a portable smart light-controllable device for tumor immunotherapy

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