Zhengyi Ruan

GATA3 Encapsulated by Tumor-Associated Macrophage-Derived Extracellular Vesicles Promotes Immune Escape and Chemotherapy Resistance of Ovarian Cancer Cells by Upregulating the CD24/Siglec-10 Axis

Tumor-associated macrophages (TAMs) possess great potential in the development of ovarian cancer (OC). Aberrant GATA-binding protein-3 (GATA3) expression has been found in TAM-derived extracellular vesicles (EVs). This study is intended to investigate the regulatory mechanism of TAM-derived EVs, expressing GATA3 in immune escape and chemotherapy resistance of OC cells.

CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein

Background Cancer immune escape is a main obstacle in designing effective anticancer therapeutic approaches. Our work was aimed to explore the function of cullin 3 (CUL3) in ovarian cancer cell immune escape and chemosensitivity. Method Gain and loss of function assays were conducted to investigate the interactions among CUL3, speckle type POZ protein (SPOP) and programmed death ligand-1 (PD-L1) as well as their effects on ovarian cell malignant phenotypes and chemosensitivity. A mouse model of xenografted ovarian cells was further established for in vivo substantiation. Result Poorly-expressed CUL3 and SPOP were found in ovarian cancer. Overexpression of CUL3 reduced malignant features as well as immune escape of ovarian cancer cells but enhanced chemosensitivity. Functionally, CUL3 degraded PD-L1 protein by forming complex with SPOP. Overexpression of CUL3 inhibited tumor formation and enhanced chemosensitivity of ovarian cancer cells in mice by degrading PD-L1 protein. Conclusion All in all, CUL3/SPOP formed a complex to promote PD-L1 degradation to inhibit ovarian cancer cell immune escape and increase chemosensitivity, offering a therapeutic target for ovarian cancer treatment.