IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver

Objective:Therapy for hepatocellular carcinoma(HCC)is a major challenge,and targeted therapies provide only a modest benefit in terms of overall survival.Treatment with antibodies to programmed cell death protein 1(PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20%of patients with advanced HCC.Novel approaches are urgently needed to treat HCC and to augment the efficacy of immunotherapy.Methods:Tumor-bearing mice were treated with Agrocybe aegerita galectin(AAGL)alone or in combination with anti-PD-1,and the tumor sizes and lifespans of mice were determined.Transcriptome analysis,cytokine analysis,flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen,and molecular and cellular analyses of tumors were used to define the underlying mechanisms.Results:AAGL significantly inhibited the growth of liver tumors in a dose-dependent manner.Furthermore,AAGL increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers;this effect was associated with the activation and migration of T cells and macrophages,in agreement with the in vitro results.Importantly,the aggregation of T cells and macrophages induced by AAGL in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade immunotherapy.Conclusions:The results showed that AAGL induced the activation and migration of lymphocytes to the liver,and that the combination of AAGL and anti-PD-1 may be a promising strategy for HCC treatment.