Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39 C gdTreg in human colorectal cancer (CRC). CD39 C gdTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4 C or CD8 C Tregs via the adenosine-mediated pathway but independent of TGF-b or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network. We further demonstrate that tumor-derived TGF-b1 induces CD39 C gdT cells from paired normal colon tissues to produce more adenosine and become potent immunosuppressive T cells. Moreover, CD39 C gdTreg infiltration is positively correlated with TNM stage and other unfavorable clinicopathological features, implicating that CD39 C gdTregs are one of the key players in establishment of immunosuppressive TME in human CRC that may be critical for tumor immunotherapy.

Histone methylation is one of the most important chromatin posttranslational modifications. It has a range of influences on nuclear functions including epigenetic inheritance, transcriptional regulation and the maintenance of genome integrity. Changes in histone methylation status take part in various physiological and pathological processes. KDM5B (lysine demethylase 5B, also called JARID1B or PLU-1) encodes the histone H3 lysine4 (H3K4) demethylase and exhibits a strong transcriptional repression activity. KDM5B plays a role in cell differentiation, stem cell self-renewal and other developmental progresses. Recent studies showed that KDM5B expression was increased in breast, bladder, lung, prostate and many other tumors and promotes tumor initiation, invasion and metastasis. Given its association with tumor progression and prognosis of cancer patients, KDM5B was proposed to be a novel target for the prevention and treatment of human cancers. In this review, we will summarize recent advances in our understanding of the regulation and function of KDM5B in development and cancer.

Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in‐vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF‐α‐treated NPCs, as indicated by β‐gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP‐3), metalloproteinase 13 (MMP‐13) and a disintegrin‐like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS‐4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF‐α‐induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF‐α‐treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.