Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.

Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease

Angiopoietin-like protein 2(ANGPTL2)stimulates inflammation and is important in the pathogenesis of diabetic kidney disease(DKD).Irbesartan is helpful in reducing diabetes-induced renal damage.In this study,the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined.Wistar rats were divided into normal,DKD,and DKD+irbesartan groups.The DKD+irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage.The 24-h urinary albumin was determined each week,renal pathological changes were observed,and expression of ANGPTL2 and nuclear factor-kappa B(NF-κB)in rat renal tissue was assessed by immunohistochemistry.Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations(0,25,50,and 75ºg/mL).Expression of ANGPTL2 and phosphorylated IκB-αwas assessed by Western blotting.The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1(MCP-1)were assessed by real-time polymerase chain reaction.The DKD rats displayed proteinuria,podocyte injury,and increased ANGPTL2 and NF-κB expression.All were relieved by irbesartan treatment.In podocytes cultured in elevated glucose,ANGPTL2 and phosphorylated IκB-αwere overexpressed at the protein level,and ANGPTL2 and MCP-1 were highly expressed at the mRNA level.Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level.The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.