Mno Nanoenzyme Armed CAR-NK Cells Enhance Solid Tumor Immunotherapy by Alleviating the Immunosuppressive Microenvironment.

Adoptively transferred cells usually suffer from exhaustion, limited expansion, and poor infiltration, partially attributing to the complicated immunosuppressive microenvironment of solid tumors. Therefore, it is necessary to explore more effective strategies to improve the poor tumor microenvironment (TME) to efficaciously deliver and support extrinsic effector cells in vivo. Herein, an intelligent biodegradable hollow manganese dioxide nanoparticle (MnO) that possesses peroxidase activity to catalyze excess HO in the TME to produce oxygen and relieve the hypoxia of solid tumors is developed.

Aryl hydrocarbon receptor (AhR) regulates adipocyte differentiation by assembling CRL4B ubiquitin ligase to target PPARγ for proteasomal degradation.

Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of adipogenesis, and its dysregulation is linked to obesity and metabolic diseases. Identification of the factors that regulate PPARγ expression and activity is therefore crucial for combating obesity. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a known role in xenobiotic detoxification.

Upregulation of IL-6 in CUL4B-deficient myeloid-derived suppressive cells increases the aggressiveness of cancer cells.

Cancer progression depends on a tumor-supportive microenvironment. Myeloid-derived suppressor cells (MDSCs) represent key cellular components in tumor microenvironment and have been demonstrated to facilitate tumor progression by restricting host immune responses and by sustaining the malignancy of cancer cells. CUL4B, which assembles the CUL4B-RING E3 ligase complex (CRL4B), possesses a potent oncogenic property in cancer cells by epigenetically inactivating many tumor suppressors.