ABSTRACT
Objective:To investigate the potential molecular mechanisms of liver cancer cell-derived secretory autophagosomes, extracellular vesicles expressing LC3B (LC3B + EVs), in promoting the exhaustion of CD8 + T cells. Methods:The proportions of LC3B + EVs and PD-1 + CD8 + T cells in peripheral blood and ascites of liver cancer patients were measured by flow cytometry. Spearman correlation test was used to analyze the correlation between the proportions of LC3B + EVs and PD-1 + CD8 + T cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with LC3B + EVs or heat shock protein 90α (HSP90α) blocking antibody-pretreated LC3B + EVs for 72 h in the presence of αCD3/CD28 antibodies and IL-2 in vitro. The proportions of PD-1 + CD8 + T and IFN-γ + CD8 + T cells and the concentrations of IL-2, TNF-α and IFN-γ in the supernatants were all detected by flow cytometry. Results:The proportions of LC3B + EVs and HSP90α + LC3B + EVs in plasma and ascites from liver cancer patients were significantly higher than those in healthy control group and non-cancerous ascites group. The level of plasma LC3B + EVs, especially HSP90α + LC3B + EVs, was significantly correlated with the percentage of exhausted PD-1 + CD8 + T cells. In addition, LC3B + EVs from human liver cancer cells up-regulated the percentage of exhausted CD8 + T cells in vitro. However, LC3B + EVs pretreated with HSP90α blocking antibody could significantly inhibit LC3B + EVs-induced CD8 + T cell exhaustion. Conclusions:Liver cancer cell-derived LC3B + EVs could effectively induce CD8 + T cell exhaustion mainly through the membrane-bound HSP90α.
ABSTRACT
Objective To investigate the clinical features, diagnosis and treatment of colorectal cancer in patients with incarcerated extracorporeal hernia. Methods The clinical manifestations, diagnosis and treatment of 9 cases of incarcerated hernias combined with colorectal cancer from January 2012 to December 2017 were retrospectively analyzed. Results All the patients were treated with surgery. Three cases underwent Hartmann surgery and incarcerated release, high ligation of hernia sac; 2 cases underwent tumor resection and tension-free hernia repair; 1 case underwent necrotic bowel resection, tumor resection and ileal stoma and tension-free hernia repair; 1 case underwent transverse colostomy and incarcerated release, high cyst ligation; 1 case underwent tension-free hernia repair and limited colon cancer radical resection; 1 case underwent high ligation of the hernia sac and limited tumor resection. Intraoperative and postoperative pathology confirmed that this group was all incarcerated abdominal hernia combined with colorectal cancer. There were 4 patients misdiagnosed before surgery. Conclusions The diagnosis and treatment often ignore the presence of colorectal cancer due to the typical clinical manifestations of incarcerated abdominal hernia. The preoperative misdiagnosis rate is high. Completing CT scans before surgery can help clarify the diagnosis and select a reasonable surgical approach.
ABSTRACT
Tumor necrosis factor-α induced protein 8 family is a group of newly discovered proteins induced by tumor necrosis factor-α. This protein family owns four highly homologous members:TIPE, TIPE1, TIPE2, TIPE3. With the deepening of the research, we found that TNFAIP8 family plays an important role in cell apoptosis, signal transduction, invasion and metastasis of tumor cell proliferation. This paper reviews the structure, mechanism, and biological function of the TNFAIP8 family.
ABSTRACT
Tumor necrosis factor-α induced protein 8 family is a group of newly discovered proteins induced by tumor necrosis factor-α. This protein family owns four highly homologous members:TIPE, TIPE1, TIPE2, TIPE3. With the deepening of the research, we found that TNFAIP8 family plays an important role in cell apoptosis, signal transduction, invasion and metastasis of tumor cell proliferation. This paper reviews the structure, mechanism, and biological function of the TNFAIP8 family.