The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%–10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigen-presenting activity scores of various antigen-presenting cells, the mitogen-activated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3highCD16lowKLRG1high natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways—including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP—were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3highCD16lowKLRG1high NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine.
Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemotherapy resistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between PTEN gene polymorphism and breast chemotherapy resistance in the Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemotherapy sensitive cases and 77 chemotherapy resistant cases. rs786204926 of the PTEN gene was analysed by Sanger sequence and Sequenom MassArray typing technology. Furthermore, we used silicon analysis to predict whether polymorphism affect the process of alternative splicing and to analyze how it affects. Results In genotyping and allelic analysis, there was a significant association between rs786204926 polymorphism and breast cancer chemotherapy resistance. Carrying the G allele or AG genotype will reduce the risk of breast cancer-based resistance to chemotherapy with anthracyclines. Silicon analysis showed that the mutation of rs786204926 produced a new receptor site, which might affect alternative splicing of PTEN gene. Conclusions We speculate that the mechanism of breast cancer chemotherapy resistance might be caused by a change in the alternative splicing caused by the rs786204926 of the PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.
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