Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

A feed-forward cycle exists in female mice after continuous HFD stress as demonstrated by increased adiposity and progressive inflammation in adipose tissue across generations. DNA hypomethylation over generations lead to epigenetically altered expression of Tlr1, Tlr2 and Lat, which may contribute to the inflammation in adipose tissue. Our study provides a potential mechanism for enhanced inflammation in adipose tissue under multigenerational HFD-fed stress.

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in non-small-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR-4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment.