Browsing by Author "Yan, Dehong"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy
    (Springer Nature, 2025) Ibrahim, Abdulrahman; Mohamady Farouk Abdalsalam, Nada; Liang, Zihao; Tariq, Hafiza Kashaf; Li, Rong; Afolabi, Lukman O.; Rabiu, Lawan; Chen, Xuechen; Xu, Shu; Xu, Zhiming; Wan, Xiaochun; Yan, Dehong; Pediatrics, School of Medicine
    Despite the success of cancer immunotherapy in treating hematologic malignancies, their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment (TME), which is mainly formed by myeloid-derived suppressor cells (MDSCs). MDSCs not only exert potent immunosuppressive effects that hinder the success of immune checkpoint inhibitors (ICIs) and adaptive cellular therapies, but they also promote tumor advancement through non-immunological pathways, including promoting angiogenesis, driving epithelial-mesenchymal transition (EMT), and contributing to the establishment of pre-metastatic environments. While targeting MDSCs alone or in combination with conventional therapies has shown limited success, emerging evidence suggests that MDSC checkpoint blockade in combination with other immunotherapies holds great promise in overcoming both immunological and non-immunological barriers. In this review, we discussed the dual roles of MDSCs, with a particular emphasis on their underexplored checkpoints blockade strategies. We discussed the rationale behind combination strategies, their potential advantages in overcoming MDSC-mediated immunosuppression, and the challenges associated with their development. Additionally, we highlight future research directions aimed at optimizing combination immunotherapies to enhance cancer therapeutic effectiveness, particularly in solid tumor therapies where MDSCs are highly prevalent.
  • Thumbnail Image
    Item
    Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma
    (Frontiers Media, 2025-01-14) Liu, Junchen; Dai, Kun; Saliu, Muhammad Auwal; Salisu, Mansur Dabai; Gan, Jiangyu; Afolabi, Lukman Olalekan; Yan, Dehong; Zhang, Guizhong; Liu, Maoxuan; Wan, Xiaochun; Pediatrics, School of Medicine
    Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage. To enhance the effectiveness of NKG2D CAR-T therapy, we investigated the potential of combining NKG2D CAR-T with approved drugs that cross the blood-brain barrier and augment NKG2D ligands expression in glioma cells. We found that sodium valproate (VPA), an antiepileptic drug, significantly increased surface NKG2D ligands expression on glioblastoma cells at a sublethal concentration. VPA treatment enhanced the susceptibility of glioblastoma cells to NKG2D CAR-T mediated cytotoxicity in both 2D monolayer and 3D tumor spheroid models in vitro. Moreover, VPA-treated glioblastoma cells stimulated CAR-T cells to produce higher levels of inflammatory cytokines (IL-2, IFN-γ, and IL-6). Mechanistically, VPA upregulated NKG2D ligands expression via the PI3K/Akt signaling pathway. Additionally, VPA treatment augmented the antitumor activity of NKG2D CAR-T cells in a glioblastoma xenograft model in vivo. These preclinical results suggest that combining VPA with NKG2D CAR-T therapy represents a promising strategy for improving glioblastoma treatment, warranting further clinical investigation.