Renal clear cell carcinoma (ccRCC) and the tumor microenvironment (TME) influence each other, leading to the tumor microenvironment that can guide the corresponding treatment. With the deepening of research, some treatment options have achieved good results, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, and so on. As the link between TME and malignancy is constantly discovered, more targeted studies on different components of TME are increasing, and this targeted therapy is a new method for treating ccRCC, and also a current research hotspot. This review summarizes the characteristics of the ccRCC tumor microenvironment, the outcomes of different treatments, and some potential targets.

BACKGROUND: Overall survival (OS) is a key endpoint measure in the management of patients with cancer. Immunotherapy has become a dominant strategy in cancer therapy. To investigate the relationship between OS and the immune system, we assessed the role of immune genes in OS in 8648 patients across 22 cancer types.
METHODS: Gene expression data and clinical information were collected from The Cancer Genome Atlas (TCGA) and cBioPortal. Survival analysis was performed with a Cox proportional hazards regression model.
RESULTS: (1) The number of prognostic genes, prognostic immune genes (PIGs) and the hazard ratio (HR) of PIGs in different cancer types all varied greatly; (2) KEGG pathway enrichment analyses indicated that the prognostic genes of 6 cancer types were significantly enriched in multiple (≥5) immune system-related pathways. Of the PIGs in these 6 cancer types, we screened 48 common PIGs in at least 5 cancer types. Eleven out of the 48 PIGs were found to participate in the T cell receptor (TCR) signaling pathway according to the STRING database. Among these genes, ZAP70, CD3E, CD3G, CD3D, and CD247 were part of the TCR \'signal-triggering module\'; (3) High expression of the PIGs involved in the TCR signaling pathway was associated with improved OS in 5 cancer types (breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), and sarcoma (SARC)), but was associated with decreased OS in brain lower-grade glioma (LGG).
CONCLUSIONS: The TCR signaling pathway played a distinct role in the OS of these 6 cancer types.

Itch or itchy E3 ubiquitin ligase was initially discovered by genetic studies on the mouse coat color changes, and its deletion results in an itchy phenotype with constant skin scratching and multi-organ inflammation. It is a member of the homologous to E6-associated protein C-terminus (HECT)-type family of E3 ligases, with the protein-interacting WW-domains for the recruitment of substrate and the HECT domain for the transfer of ubiquitin to the substrate. Since its discovery, numerous studies have demonstrated that Itch is involved in the control of many aspects of immune responses including T-cell activation and tolerance and T-helper cell differentiation. Itch is also implicated in other biological contexts such as tumorigenesis, development, and stress responses. Many signaling pathways are regulated by Itch-promoted ubiquitylation of diverse target proteins. Itch is also involved in human diseases. Here, we discuss the major progress in understanding the biological significance of Itch-promoted protein ubiquitylation in the immune and other systems and in Itch-mediated regulation of signal transduction.