Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and asso...Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells.The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1(PD-L1)on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system,including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy.These cells also produce modest levels of cytokines during exhaustion,tumor-infiltrating T CD4+cells with high levels of PD-1 and CD39 release considerable quantities of cytokines.The Wnt/β-catenin signaling pathway,which controls the expression of genes involved in the tumor cells’markers,is demonstrated to be one of the most potent cancer stimulants.It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells.PD-L1,as an inhibitory immune checkpoint,is essential for controlling immune system activity by inhibiting T-cells’inflammatory function.In the present review,we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy.We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.展开更多
Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2...Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.展开更多
基金supported by the Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iran.
文摘Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells.The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1(PD-L1)on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system,including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy.These cells also produce modest levels of cytokines during exhaustion,tumor-infiltrating T CD4+cells with high levels of PD-1 and CD39 release considerable quantities of cytokines.The Wnt/β-catenin signaling pathway,which controls the expression of genes involved in the tumor cells’markers,is demonstrated to be one of the most potent cancer stimulants.It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells.PD-L1,as an inhibitory immune checkpoint,is essential for controlling immune system activity by inhibiting T-cells’inflammatory function.In the present review,we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy.We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.
文摘Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.
