The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ...The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ER （endoplasmic reticulum） lumen where the antigenic peptides are loaded onto the HLA class I molecules. Recently, numerous studies show that TAP is closely related with various diseases such as viral infections, autoimmune diseases, and different malignancies. In consideration of important roles of TAP in human adaptive immunity, this review summarizes the recent advances in structure-function relationships of crucial domains and transport mechanism systematically. The challenging problems and potential methods are also pointed out for in-depth researches.展开更多
Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor imm...Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.展开更多
基金Supported by Programme of Introducing Talents of Discipline to Universities(‘111’project)the Key Natural Science Foundation of Chongqing(CSTC,2009BA5068)the Fundamental Research Funds for the Central Universities(CDJXS,11231177)
文摘The transporter associated with antigen processing （TAP） belongs to the ATP-binding cassette （ABC） transporter superfamily. Driven by ATP hydrolysis, TAP translocates antigenic peptides from the cytosol into the ER （endoplasmic reticulum） lumen where the antigenic peptides are loaded onto the HLA class I molecules. Recently, numerous studies show that TAP is closely related with various diseases such as viral infections, autoimmune diseases, and different malignancies. In consideration of important roles of TAP in human adaptive immunity, this review summarizes the recent advances in structure-function relationships of crucial domains and transport mechanism systematically. The challenging problems and potential methods are also pointed out for in-depth researches.
基金Supported by(in part)Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B(No.17fk0310116h0001) from the Japan Agency for Medical Research and Development(AMED)Extramural Collaborative Research Grant of Cancer Research Institute,Kanazawa University
文摘Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.
