Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the ...Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the parasite can exert several immune suppressive mechanisms that facilitate escaping the immune responses.One of these mechanisms is the up-regulation of programmed death-1/programmed death ligand-1 pathway which causes T cells to undergo exhaustion.Autophagy is strongly linked to the immune response,with some research indicating that activating autophagy reduces the immune response to some intracellular pathogens,while others indicate that activating autophagy limits the growth of intracellular pathogens.Leishmania was found to subvert the host defense mechanisms for its own persistence,such as Leishmania-induced autophagy modulation.Leishmania was reported to activate autophagy in different studies,thus getting a dual benefit by evading the immune system and simultaneously utilizing the autophagy byproducts as nutrients.In this review,we introduced different immune evasion/suppressive mechanisms used by Leishmania,and different immunotherapies which were developed accordingly.We focused on the programmed death-1/programmed death ligand-1 pathway as well as autophagy with the potential interplay of both mechanisms.展开更多
Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of ne...Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.展开更多
目的探讨外周T细胞淋巴瘤(peripheral T cell lymphoma,PTCL)患者肿瘤组织中程序性细胞死亡受体1(programmed cell death-1,PD-1)和程序性细胞死亡受体1配体(programmed death ligand 1,PD-L1)蛋白的表达情况,分析其与患者预后的关系。...目的探讨外周T细胞淋巴瘤(peripheral T cell lymphoma,PTCL)患者肿瘤组织中程序性细胞死亡受体1(programmed cell death-1,PD-1)和程序性细胞死亡受体1配体(programmed death ligand 1,PD-L1)蛋白的表达情况,分析其与患者预后的关系。方法采用免疫组化法检测PTCL患者肿瘤组织中PD-1、PD-L1蛋白的表达,并分析其表达与患者临床分期、疗效及预后之间的关系。结果 PTCL患者肿瘤组织中PD-1蛋白的表达阳性率为35%,PD-L1蛋白的阳性率为70%,炎性淋巴结组织中未见PD-1、PD-L1表达,PD-1、PD-L1蛋白的表达与患者临床分期正相关,PD-1蛋白的表达与疗效负相关,PD-1与PD-L1蛋白双阳性的PTCL患者生存期明显缩短。结论PTCL患者淋巴瘤组织中PD-1和PD-L1蛋白表达阳性率高于炎性淋巴结组织,是预后不良的指标。展开更多
Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment...Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment for bladder cancer. However, the use of this treatment has clinical disadvantages such as small overall benefit, toxic effects on the target population, and inability to select the most beneficial patients. This phenomenon has been improved by the presence of immunological checkpoint inhibitors, of which PD-1/PDL-1 inhibitors are one of them. The use of PD-1/ PD-L1 in urinary cancer is a new treatment and offers new hope for the treatment of platinum-refractory metastatic urothelial bladder cancer. Related drugs have now been approved for use in patients with refractory or unqualified platinum-based chemotherapy drugs. Clinical trials are currently underway to determine how best to use these drugs, and whether they should be used alone or in combination with other treatments. This article will review the research progress of PD-1/PDL-1 inhibitors in bladder tumors.展开更多
The current treatments of liver cancer in China are mainly comprehensive treatment and systematic treatment, with poor therapeutic effect and high recurrence rate and metastasis rate. The existence of immunosuppressiv...The current treatments of liver cancer in China are mainly comprehensive treatment and systematic treatment, with poor therapeutic effect and high recurrence rate and metastasis rate. The existence of immunosuppressive microenvironment is an important reason for liver tumor cells to escape from the host immune system, and also an important basis for the occurrence and development of liver cancer. With the recent transformation of the target of tumor therapy from tumor cells to tumor cell immune microenvironment, immunotherapy has emerged quietly. It is a new strategy for the treatment of hepatocellular carcinoma to improve the immune attack on tumor cells by changing the immunosuppressive environment of hepatocellular carcinoma cells. Immune checkpoint is the main mechanism by which liver cancer cells escape the host immune system. PD-1/PDL-1 and CTLA-4 are targeted immunocheckpoint inhibitors, which have shown good therapeutic effects and application prospects in the clinical treatment of HCC. This article reviews the latest advances in immunocheckpoint inhibitors in the immunotherapy of hepatocellular carcinoma.展开更多
文摘Leishmania donovani is one of the causative agents of visceral leishmaniasis.The immune response against Leishmania depends on CD4^(+)T helper type 1 cells.The immune system is unable to combat Leishmania because the parasite can exert several immune suppressive mechanisms that facilitate escaping the immune responses.One of these mechanisms is the up-regulation of programmed death-1/programmed death ligand-1 pathway which causes T cells to undergo exhaustion.Autophagy is strongly linked to the immune response,with some research indicating that activating autophagy reduces the immune response to some intracellular pathogens,while others indicate that activating autophagy limits the growth of intracellular pathogens.Leishmania was found to subvert the host defense mechanisms for its own persistence,such as Leishmania-induced autophagy modulation.Leishmania was reported to activate autophagy in different studies,thus getting a dual benefit by evading the immune system and simultaneously utilizing the autophagy byproducts as nutrients.In this review,we introduced different immune evasion/suppressive mechanisms used by Leishmania,and different immunotherapies which were developed accordingly.We focused on the programmed death-1/programmed death ligand-1 pathway as well as autophagy with the potential interplay of both mechanisms.
基金Fondazione Italiana Sclerosi Multipla(ref.2015/R/16 to PM)by Elena Pecci research project and Fondazione Careggi Onlus.
文摘Multiple sclerosis is an autoimmune disease characterised by a chronic inflammation within the central nervous system. In the last ten years, studies on multiple sclerosis have been concentrated on the discovery of new biomarkers of disease and potential therapeutic targets. In chronic infection or in cancer, the immune system response is faulty and maintained in a condition defined as T-cell exhaustion induced by expression of co-inhibitory receptors. The PD-1/PDL-1 pathway is demonstrated to be the main one responsible for promoting T-cell exhaustion, and immunotherapies targeting PD-1 or PDL-1 have shown beneficial clinical outcomes in several tumours and chronic diseases. Contrarily, transcriptional T-cell exhaustion signature and high expression of co-inhibitor receptor PD-1 are associated with favourable prognosis in multiple sclerosis and other autoimmune diseases. Several studies have clearly demonstrated PD-1 has a dual role in immune self-tolerance: to constrain autoreactive T cells in anergic condition and to protect the tissue from the damage caused by the activation of endogenous autoreactive T cells. Consequently, immune checkpoint inhibitor therapies that target inhibitory receptors in cancer cause an exacerbation of autoimmune diseases. This review describes the roles of the PD-1/ PDL-1 pathway in cancer and autoimmune diseases, especially in multiple sclerosis, and how manipulating PD-1 can be a therapeutic approach in multiple sclerosis.
文摘目的探讨外周T细胞淋巴瘤(peripheral T cell lymphoma,PTCL)患者肿瘤组织中程序性细胞死亡受体1(programmed cell death-1,PD-1)和程序性细胞死亡受体1配体(programmed death ligand 1,PD-L1)蛋白的表达情况,分析其与患者预后的关系。方法采用免疫组化法检测PTCL患者肿瘤组织中PD-1、PD-L1蛋白的表达,并分析其表达与患者临床分期、疗效及预后之间的关系。结果 PTCL患者肿瘤组织中PD-1蛋白的表达阳性率为35%,PD-L1蛋白的阳性率为70%,炎性淋巴结组织中未见PD-1、PD-L1表达,PD-1、PD-L1蛋白的表达与患者临床分期正相关,PD-1蛋白的表达与疗效负相关,PD-1与PD-L1蛋白双阳性的PTCL患者生存期明显缩短。结论PTCL患者淋巴瘤组织中PD-1和PD-L1蛋白表达阳性率高于炎性淋巴结组织,是预后不良的指标。
基金The National Natural Science Foundation of China.Project No:81672519.
文摘Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment for bladder cancer. However, the use of this treatment has clinical disadvantages such as small overall benefit, toxic effects on the target population, and inability to select the most beneficial patients. This phenomenon has been improved by the presence of immunological checkpoint inhibitors, of which PD-1/PDL-1 inhibitors are one of them. The use of PD-1/ PD-L1 in urinary cancer is a new treatment and offers new hope for the treatment of platinum-refractory metastatic urothelial bladder cancer. Related drugs have now been approved for use in patients with refractory or unqualified platinum-based chemotherapy drugs. Clinical trials are currently underway to determine how best to use these drugs, and whether they should be used alone or in combination with other treatments. This article will review the research progress of PD-1/PDL-1 inhibitors in bladder tumors.
文摘The current treatments of liver cancer in China are mainly comprehensive treatment and systematic treatment, with poor therapeutic effect and high recurrence rate and metastasis rate. The existence of immunosuppressive microenvironment is an important reason for liver tumor cells to escape from the host immune system, and also an important basis for the occurrence and development of liver cancer. With the recent transformation of the target of tumor therapy from tumor cells to tumor cell immune microenvironment, immunotherapy has emerged quietly. It is a new strategy for the treatment of hepatocellular carcinoma to improve the immune attack on tumor cells by changing the immunosuppressive environment of hepatocellular carcinoma cells. Immune checkpoint is the main mechanism by which liver cancer cells escape the host immune system. PD-1/PDL-1 and CTLA-4 are targeted immunocheckpoint inhibitors, which have shown good therapeutic effects and application prospects in the clinical treatment of HCC. This article reviews the latest advances in immunocheckpoint inhibitors in the immunotherapy of hepatocellular carcinoma.
