The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical r...The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical role against these diseases,whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo,poor penetration across biological barriers,and rapid clearance by the reticuloendothelial system.Drug delivery strategies are potent to promote their delivery.Herein,we reviewed the potential targets for immunotherapy against the major infammatory diseases,discussed the biologics and drug delivery systems involved in the immunotherapy,particularly highlighted the approved therapy tactics,and finally offer perspectives in this feld.展开更多
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with a...Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma? Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.展开更多
Cancer immunotherapy has become a new generation of anti-tumor treatment,but its indications still focus on several types of tumors that are sensitive to the immune system.Therefore,effective strategies that can expan...Cancer immunotherapy has become a new generation of anti-tumor treatment,but its indications still focus on several types of tumors that are sensitive to the immune system.Therefore,effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy.Natural products are reported to have this effect on cancer immunotherapy,including cancer vaccines,immune-check points inhibitors,and adoptive immune-cells therapy.And the mechanism of that is mainly attributed to the remodeling of the tumorimmunosuppressive microenvironment,which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy.Therefore,this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism.And we found that saponins,polysaccharides,and flavonoids are mainly three categories of natural products,which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment.Besides,this review also collected the studies about nano-technology used to improve the disadvantages of natural products.All of these studies showed the great potential of natural products in cancer immunotherapy.展开更多
Natural killer cells （NKs） have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including...Natural killer cells （NKs） have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells （PBMCs）, stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.展开更多
Liver transplantation(LT)has emerged as a curative strategy for hepatocellular carcinoma(HCC),but contributes to a higher predisposition to HCC recurrence in the immunosuppression context,especially for tumors beyond ...Liver transplantation(LT)has emerged as a curative strategy for hepatocellular carcinoma(HCC),but contributes to a higher predisposition to HCC recurrence in the immunosuppression context,especially for tumors beyond the Milan criteria.Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors,including HCC,it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection.Nevertheless,accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC,from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting.Generally,immunotherapy mainly includes immune checkpoint inhibitors(ICIs),adoptive cell transfer(ACT)and vaccine therapy.ICIs,followed by ACT,have been most investigated in LT,with some promising results.Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy,it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients.In addition,the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT.In this review,we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC.Moreover,we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.展开更多
The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells （MDSCs） could prevent the concanavalin A （ConA）- induce...The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells （MDSCs） could prevent the concanavalin A （ConA）- induced hepatitis through suppressing T cell proliferation. We observed an increase in the frequencies of MDSCs in mouse spleen and liver at early stage of ConA treatment, implicating that the MDSCs might be involved in the initial resistance of mice against ConA- mediated inflammation. Subpopulation analysis showed that the MDSCs in liver of ConA-induced mice were mainly granulocytic MDSCs. Adoptive transfer of the bone marrow-derived MDSCs into ConA-treated mice showed that the MDSCs migrated into the liver and spleen where they suppressed T cell proliferation through ROS pathway. In addition, the frequencies of MDSCs in mice were also significantly increased by the treatment with immune suppressor glucocorticoids. Transfer of MDSCs into the regulatory T cell （Treg）- depleted mice showed that the protective effect of MDSCs on ConA-induced hepatitis is Treg-independent. In conclusion, our results demonstrate that MDSCs possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease.展开更多
Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significan...Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this, focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T call receptor （TCR） gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers. Cellular ＆ Molecular Immunology.展开更多
Inflammation is a major underlying mechanism in the progression of numerous cardiovascular diseases(CVDs).Regulatory T cells(Tregs)are typical immune regulatory cells with recognized immunosuppressive properties.Despi...Inflammation is a major underlying mechanism in the progression of numerous cardiovascular diseases(CVDs).Regulatory T cells(Tregs)are typical immune regulatory cells with recognized immunosuppressive properties.Despite the immunosuppressive properties,researchers have acknowledged the significance of Tregs in maintaining tissue homeostasis and facilitating repair/regeneration.Previous studies unveiled the heterogeneity of Tregs in the heart and aorta,which expanded in CVDs with unique transcriptional phenotypes and reparative/regenerative function.This review briefly summarizes the functional principles of Tregs,also including the synergistic effect of Tregs and other immune cells in CVDs.We discriminate the roles and therapeutic potential of Tregs in CVDs such as atherosclerosis,hypertension,abdominal arterial aneurysm,pulmonary arterial hypertension,Kawasaki disease,myocarditis,myocardial infarction,and heart failure.Tregs not only exert anti-inflammatory effects but also actively promote myocardial regeneration and vascular repair,maintaining the stability of the local microenvironment.Given that the specific mechanism of Tregs functioning in CVDs remains unclear,we reviewed previous clinical and basic studies and the latest findings on the function and mechanism of Tregs in CVDs.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 82073782)the Double FirstClass(CPU2018PZQ13,China)of the China Pharmaceutical University,the Shanghai Science and Technology Committee(No.19430741500,China)+1 种基金the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Start-up Grant from City University of Hong Kong(No.9610472,China)。
文摘The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical role against these diseases,whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo,poor penetration across biological barriers,and rapid clearance by the reticuloendothelial system.Drug delivery strategies are potent to promote their delivery.Herein,we reviewed the potential targets for immunotherapy against the major infammatory diseases,discussed the biologics and drug delivery systems involved in the immunotherapy,particularly highlighted the approved therapy tactics,and finally offer perspectives in this feld.
基金grants from the National Natural Science Foundation of China (Nos.31571434.81874155, and 81872482)the National Science and Technology Major Project (No.2015CB553701).
文摘Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma? Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.
基金supported by Science and Technology Plan Project of Shenyang(RC200406,China)the Career Development Program for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(Shenyang,China)。
文摘Cancer immunotherapy has become a new generation of anti-tumor treatment,but its indications still focus on several types of tumors that are sensitive to the immune system.Therefore,effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy.Natural products are reported to have this effect on cancer immunotherapy,including cancer vaccines,immune-check points inhibitors,and adoptive immune-cells therapy.And the mechanism of that is mainly attributed to the remodeling of the tumorimmunosuppressive microenvironment,which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy.Therefore,this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism.And we found that saponins,polysaccharides,and flavonoids are mainly three categories of natural products,which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment.Besides,this review also collected the studies about nano-technology used to improve the disadvantages of natural products.All of these studies showed the great potential of natural products in cancer immunotherapy.
基金This work was supported by the National Natural Science Foundation of China （Nos. 81788101, 91542000, 81671558, and 31571440） the Ministry of Science and Technology of China （No. 2016YFC1303503） and Chinese Academy of Sciences （Nos. XDA12020312, XDPB030301, and XDPB030303）.
文摘Natural killer cells （NKs） have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells （PBMCs）, stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.
基金National Natural Science Foundation of China,No.81702923 and No.81871262.
文摘Liver transplantation(LT)has emerged as a curative strategy for hepatocellular carcinoma(HCC),but contributes to a higher predisposition to HCC recurrence in the immunosuppression context,especially for tumors beyond the Milan criteria.Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors,including HCC,it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection.Nevertheless,accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC,from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting.Generally,immunotherapy mainly includes immune checkpoint inhibitors(ICIs),adoptive cell transfer(ACT)and vaccine therapy.ICIs,followed by ACT,have been most investigated in LT,with some promising results.Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy,it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients.In addition,the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT.In this review,we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC.Moreover,we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.
基金ACKNOWLEDGEMENTS This work was supported by grants from the National Basic Research Program （973 Program） （Nos. 2012CB517603 and 2011CB504803）, the National Natural Science Foundation of China （Grant No. 31301061）, the Natural Science Foundation of Jiangsu Province （No. BK2011013 and BK20130564）, and the Specialized Research Fund for the Doctoral Program of Higher Education （20130091120037）.
文摘The mechanism underlying T cell-mediated fulminant hepatitis is not fully understood. In this study, we investigated whether myeloid derived suppressor cells （MDSCs） could prevent the concanavalin A （ConA）- induced hepatitis through suppressing T cell proliferation. We observed an increase in the frequencies of MDSCs in mouse spleen and liver at early stage of ConA treatment, implicating that the MDSCs might be involved in the initial resistance of mice against ConA- mediated inflammation. Subpopulation analysis showed that the MDSCs in liver of ConA-induced mice were mainly granulocytic MDSCs. Adoptive transfer of the bone marrow-derived MDSCs into ConA-treated mice showed that the MDSCs migrated into the liver and spleen where they suppressed T cell proliferation through ROS pathway. In addition, the frequencies of MDSCs in mice were also significantly increased by the treatment with immune suppressor glucocorticoids. Transfer of MDSCs into the regulatory T cell （Treg）- depleted mice showed that the protective effect of MDSCs on ConA-induced hepatitis is Treg-independent. In conclusion, our results demonstrate that MDSCs possess a direct protective role in T cell-mediated hepatitis, and increasing the frequency of MDSCs by either adoptive transfer or glucocorticoid treatment represents a potential cell-based therapeutic strategy for the acute inflammatory disease.
文摘Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this, focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T call receptor （TCR） gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers. Cellular ＆ Molecular Immunology.
基金National Natural Science Foundation of China(Nos.82030016 and 82230011 to Xiang Cheng and No.82000443 to Jingyong Li)
文摘Inflammation is a major underlying mechanism in the progression of numerous cardiovascular diseases(CVDs).Regulatory T cells(Tregs)are typical immune regulatory cells with recognized immunosuppressive properties.Despite the immunosuppressive properties,researchers have acknowledged the significance of Tregs in maintaining tissue homeostasis and facilitating repair/regeneration.Previous studies unveiled the heterogeneity of Tregs in the heart and aorta,which expanded in CVDs with unique transcriptional phenotypes and reparative/regenerative function.This review briefly summarizes the functional principles of Tregs,also including the synergistic effect of Tregs and other immune cells in CVDs.We discriminate the roles and therapeutic potential of Tregs in CVDs such as atherosclerosis,hypertension,abdominal arterial aneurysm,pulmonary arterial hypertension,Kawasaki disease,myocarditis,myocardial infarction,and heart failure.Tregs not only exert anti-inflammatory effects but also actively promote myocardial regeneration and vascular repair,maintaining the stability of the local microenvironment.Given that the specific mechanism of Tregs functioning in CVDs remains unclear,we reviewed previous clinical and basic studies and the latest findings on the function and mechanism of Tregs in CVDs.
