The correlation between serum heat shock protein 70, soluble programmed death protein 1, 25-hydroxy vitamin D 3 levels and prognosis in patients with hepatitis B associated liver cirrhosis combined with type 2 diabetes mellitus / 中国医师进修杂志

Objective:To investigate the expression of serum heat shock protein 70 (HSP70), soluble programmed death protein 1 (sPD-1), and 25-hydroxy vitamin D 3 in hepatitis B associated liver cirrhosis (HBLC) combined with type 2 diabetes mellitus (T2DM) and their value in prognostic prediction. Methods:The clinical data of 97 patients with HBLC combined with T2DM (HBLC combined with T2DM group), 105 patients with HBLC (HBLC group) and 118 patients with T2DM (T2DM group) from June 2018 to November 2019 in Zhejiang Putuo Hospital were prospectively analyzed. The serum levels of HSP70, sPD-1 and 25-hydroxy vitamin D 3 were compared among 3 groups, and the correlation between above serum indexes and liver function indexes, blood sugar indexes were analyzed. The liver function indexes included alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the blood sugar indexes included fasting blood glucose (FBG) and glycosylated hemoglobin (HbA 1c). According to the prognosis 6 months later, the patients with HBLC combined with T2DM were divided into poor prognosis (28 cases) and good prognosis (69 cases), and the HSP70, sPD-1, 25-hydroxy vitamin D 3 and liver function Child-Pugh classification were compared. The predictive value of serum HSP70, sPD-1 and 25-hydroxy vitamin D 3 on prognosis in patients with HBLC combined with T2DM was analyzed by receiver operating characteristic (ROC) curve. Results:The HSP70 and sPD-1 in HBLC combined with T2DM group were significantly higher than those in HBLC group and T2DM group: (4.28 ± 1.19) μg/L vs. (2.27 ± 0.76) and (2.40 ± 0.84) μg/L, (7.86 ± 2.45) ng/L vs. (4.23 ± 1.62) and (3.85 ± 1.27) ng/L, the 25-hydroxy vitamin D 3 was significantly lower than that in HBLC group and T2DM group: (13.62 ± 3.96) μg/L vs. (18.63 ± 6.11) and (17.45 ± 4.36) μg/L, and there were statistical differences ( P<0.05); there were no statistical differences between HBLC group and T2DM group ( P>0.05). The Pearson correlation analysis result showeds that HSP70 and sPD-1 were positively correlated with ALT, AST, FBG and HbA 1c ( P<0.01), the 25-hydroxy vitamin D 3 was negatively correlated with ALT, AST, FBG and HbA 1c ( P<0.01) in patients with HBLC combined with T2DM. In patients with HBLC combined with T2DM, the HSP70, sPD-1 and rate of Child-Pugh classification B in patients with poor prognosis were significantly higher than those in patients with good prognosis: (6.03 ± 1.63) μg/L vs. (3.57 ± 1.02) μg/L, (9.86 ± 1.59) ng/L vs. (7.05 ± 2.62) ng/L and 71.43% (20/28) vs. 30.43% (21/69), the 25-hydroxy vitamin D 3 was significantly lower than that in patients with good prognosis: (9.26 ± 3.02) μg/L vs. (15.39 ± 5.84) μg/L, and there were statistical differences ( P<0.01 or <0.05). The ROC curve analysis result showed that the area under curve of HSP70, sPD-1 combined with 25-hydroxy vitamin D 3 in predicting prognosis was the highest in patients with HBLC combined with T2DM, which was 0.890, with a sensitivity of 89.29% and a specificity of 79.71%. Conclusions:The levels of serum HSP70 and sPD-1 in patients with HBLC combined with T2DM increase, and the level of 25-hydroxy vitamin D 3 decreases. There is a good linear relationship with liver function and blood glucose. Early combined detection of the above serum levels can provide new ideas for clinical implementation of symptomatic treatment and prognosis prediction.

Immunology of cervical cancer

ABSTRACT Optimal function of the immune system allows the recognition and elimination of infected and tumor cells. However, these cells can develop mechanisms to evade the cellular immune response. In human papillomavirus (HPV) infection, dysregulation of major histocompatibility complex Class I molecules and other components of the innate immune system promote the survival of infected cells by allowing the infection to persist which, in turn, favors the development of cancer. Further, tumor cells possess inherent mechanisms designed to block the recognition and activation of cytotoxic lymphocytes: particularly, HPV proteins such as E1 and E2 and oncoproteins E5, E6, and E7 that inhibit immune mechanisms and/or stimulate the expression of immunosuppressive cytokines. These mechanisms include a decrease in receptor activation and costimulating molecules on the surface of immune cells, as well as the constitutive expression of molecules that inhibit their function, which allow HPV persistence and tumor progression. Immunotherapy-based therapeutic options are positioned as excellent candidates for the treatment of cervical cancer.

Research progress on the application of LAG-3 and its inhibitors in cancer immunotherapy / 中国肿瘤生物治疗杂志

@# Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene, which consists of extracellular, transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand, thus avoiding autoimmunitycaused by T cell over-activation. Like programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand. With the development in research of immune checkpoints, LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4. This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy, in order to provide reference for the further study of LAG-3.

Treatment of non-small cell lung cancer comes to the age of immunotherapy / 解放军医学杂志

Immune checkpoint inhibitors have become an important alternative for advanced non-small cell lung cancer (NSCLC) patients to surgery, chemotherapy, radiotherapy and targeted therapy. Monoclonal antibodies directed against immune checkpoint have shown better results in the application of first- or second-line treatment of NSCLC and for both squamous and non-squamous cell carcinoma patients, especially for those with positive PD-L1 tumor cells. Some comments will be made in present paper about the efficacy, biomarker, combined therapy and the resistant mechanism of immune checkpoint inhibitors.