Identification of co-expressed gene networks promoting CD8+ T cell infiltration and having prognostic value in uveal melanoma.

Current immunotherapies are unsatisfactory against uveal melanoma (UM); however, elevated CD8+ T cell infiltration level indicates poor prognosis in UM. Here, we aimed to identify co-expressed gene networks promoting CD8+ T cell infiltration in UM and created a prognostic hazard model based on the identified hub genes. Raw data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Stromal-immune comprehensive score (ESTIMATE) was used to evaluate the immune-infiltration landscape of the tumor microenvironment. Single-Sample Gene Set Enrichment Analysis (ssGSEA) and Weighted Correlation Network Analysis (WGCNA) were used to quantify CD8+ T cell infiltration level and identify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to analyze the biological processes. Least absolute shrinkage and selection operator (LASSO) Cox regression were used to establish a prognostic model, which was further validated. Finally, pan-cancer analysis evaluated these genes to be associated with CD8+ T cell infiltration in other tumors. In conclusion, the proposed four-gene (PTPN12, IDH2, P2RX4, and KDELR2) prognostic hazard model had satisfactory prognostic ability. These hub genes may promote CD8+ T cell infiltration in UM through antigen presentation, and CD8+ T cell possibly function as Treg, resulting in poor prognosis. These findings might facilitate the development of novel immunotherapies.

Advances in the applications of mesenchymal stem cell-conditioned medium in ocular diseases.

Mesenchymal stem cell-conditioned medium (MSC-CM), also known as secretome, is secreted by MSC and contains a variety of bioactive factors with anti-inflammatory, anti-apoptotic, neuroprotection, and proliferation effects. Increasing evidence proved that MSC-CM plays an important role in various diseases, including skin, bone, muscle, and dental diseases. However, the role of MSC-CM in ocular diseases is not quite clear, Therefore, this article reviewed the composition, biological functions, preparation, and characterization of MSC-CM and summarized current research advances in different sources of MSC-CM in corneal and retinal diseases, including dry eye, corneal epithelial damage, chemical corneal injury, retinitis pigmentosa (RP), anterior ischemic optic neuropathy (AION), diabetic retinopathy (DR), and other retinal degenerative changes. For these diseases, MSC-CM can promote cell proliferation, reduce inflammation and vascular leakage, inhibit retinal cell degeneration and apoptosis, protect corneal and retinal structures, and further improves visual function. Hence, we summarize the production, composition and biological functions of MSC-CM and focus on describing its mechanisms in the treatment of ocular diseases. Furthermore, we look at the unexplored mechanisms and further research directions for MSC-CM based therapy in ocular diseases.

γδ T cells in autoimmune uveitis pathogenesis: A promising therapeutic target.

Autoimmune uveitis is a non-infectious, inflammatory intraocular disease that affects the uveal and adjacent tissues. It frequently causes varying degrees of visual loss. Evidence for the strong association between activated γδ T cells and the development of autoimmune uveitis is growing. The innate and adaptive immune response are connected in the early phases by the γδ T cells that contain the γ and δ chains. γδ T cells can identify antigens in a manner that is not constrained by the MHC. When activated by various pathways, γδ T cells can not only secrete pro-inflammatory factors early on (such as IL-17), but they can also promote Th17 cells responses, which ultimately exacerbates autoimmune uveitis. Therefore, we review the mechanisms by which γδ T cells affect autoimmune uveitis in different activation and disease states. Moreover, we also prospect for immunotherapies targeting different γδ T cell-related action pathways, providing a reference for exploring new drug for the treatment of autoimmune uveitis.