Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy

Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy

“…The TNF superfamily comprises molecules pivotal to the orchestration and efficacy of both innate and adaptive immune responses, making many members of this family targets for drug development in tumor immunotherapy and anti-inflammatory medication [ 219 ]. The GC-induced TNF receptor family-related protein (GITR) is an immune checkpoint molecule involved in the regulation of T cell responses [ 220 ]. The phenomenon that the single structural domain of GITR mediates its binding with ligands suggests that this unique mode of action may represent an ancient binding pattern in the evolution of the TNF/TNFR superfamily [ 221 , 222 ].…”

FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies

“…FBXW7 is involved in immune evasion that occurs in anti-tumor immune responses, as well as in the regulation of the immune microenvironment, and its mutation or downregulation is more likely to lead to immunotherapy resistance (Xing et al, 2022). Mutation or loss of function of FBXW7 significantly reduces the infiltration of dendritic cells and immune cells, such as macrophages and CD8 T cells, in the tumor microenvironment, thereby promoting resistance to anti-PD-1 therapy (Gstalder et al, 2020;Ding et al, 2023). In addition to this, FBXW7 can regulate the tumor immune microenvironment by mediating the degradation of GSK-3β phosphorylated C/EBPδ, influencing macrophage polarization toward M2-type and modulating macrophage innate immune responses Zhong et al, 2020).…”

“…Activation of FBXW7 promotes MCL-1 degradation and restores the sensitivity of drug-resistant NSCLC cells to targeted therapy (Ye et al, 2017). Recent studies have suggested that PD-1/PD-L1 protein abundance and stability may be regulated by ubiquitin-mediated proteasomal degradation (Ding et al, 2023). FBXW7 status can serve as a biomarker to predict patient response to anti-PD-1 immunotherapy in NSCLC, and an elevated expression of FBXW7 increases sensitivity to anti-PD-1 immunotherapy (Liu et al, 2022).…”

Novel Lactams as Cbl-b Inhibitors for Treating Cancer

“…The table below shows representative compounds tested for Cbl-b inhibition and the biological data obtained from testing representative examples. − …”