BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studie...Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.展开更多
Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therap...Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.展开更多
BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untr...BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untreated non-small cell lung cancer to date.CASE SUMMARY A 44-year-old nonsmoking woman presented to the hospital due to fever,palpitation,nausea,and cough for 1 mo and was diagnosed with stage cT3N3M0(IIIc)adenocarcinoma of the lung.Auxiliary examinations revealed elevated cytokine[tumor necrosis factor-α,interleukin(IL)-1β,and IL-6]and inflammatory factor levels,which decreased after treatment with corticosteroids and immunoglobulin and when tumor growth was controlled following chemotherapy,radiotherapy,and antiangiogenesis therapy.However,tumor recurrence was observed.After administration of nivolumab as third-line treatment,the patient’s condition was transiently controlled;however,CRS-like symptoms suddenly emerged,which led to a resurgence of cytokines and inflammatory factors and rapid death.CONCLUSION CRS can develop in treatment-naïve lung cancer patients.Patients with tumorrelated CRS may be at risk of CRS recurrence,aggravation,and onset of immune checkpoint inhibitor-related adverse events.展开更多
BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis...BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis(RM)followed by CART therapy treatment has not been previously reported.CASE SUMMARY We report a case of a 22-year-old woman with relapsed acute lymphoblastic leukemia obtained sequential cluster of differentiation(CD)19 and CD22 CAR-T infusion.This patient experienced grade 3 CRS with RM,mild hypotension requiring intravenous fluids,and mild hypoxia and was managed effectively with the IL-6 receptor antagonist tocilizumab.This patient had no signs of immune effector cell-associated neurologic syndrome.Restaging scans 30 d postCAR-T therapy demonstrated a complete remission,and the symptoms of muscle weakness improved through rehabilitation.CONCLUSION Myalgia is an easily overlooked symptom of severe CRS after CAR-T therapy.It is necessary to monitor myoglobin levels when a patient presents with symptoms of myalgia or acute renal insufficiency.展开更多
Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine...Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine in recent years.ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic.In order to achieve early clinical prediction and management of immune-related adverse events(irAEs),it is still necessary to perform further research on the mechanisms,risk factors,and predictors of irAE occurrence in the future.Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis.This case provides an important reference for the use of programmed cell death protein-1(PD-1)inhibitors in patients of tumours combined with chronic plaque psoriasis.This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours.PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immunerelated adverse events such as toxic epidermal necrolysis release and psoriasis.Glucocorticosteroids are the first-line agents for irAEs.The incidence of rheumatic irAEs may be higher in reality,which will inevitably become a new challenge for rheumatologists and dermatologists.展开更多
Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarka...Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.展开更多
Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described...Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune diseases.Particularly,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ dysfunction.However,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the host.Although a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear.In the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS.Considering that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.展开更多
Since the publication of this review1,the authors noticed one inadvertent mistake occurred in Fig.6c that needs to be corrected.The correct Fig.6 is provided as follows.In detail,"Human-derived CAR-T cells"h...Since the publication of this review1,the authors noticed one inadvertent mistake occurred in Fig.6c that needs to be corrected.The correct Fig.6 is provided as follows.In detail,"Human-derived CAR-T cells"has been replaced by"Mouse-derived CAR-T cells"in the revised fig.6c.The key findings of the article are not affected by these corrections.The original review article has been corrected.展开更多
OBJECTIVE:To verify the efficacy of glucocorticoids,chloroquine and vitamin A in the treatment of cytokine release syndrome(CRS),and to investigate the underlying mechanisms,based on network pharmacology.METHODS:We us...OBJECTIVE:To verify the efficacy of glucocorticoids,chloroquine and vitamin A in the treatment of cytokine release syndrome(CRS),and to investigate the underlying mechanisms,based on network pharmacology.METHODS:We used network pharmacology analysis and found 20 co-targeted genes of glucocorticoids,chloroquine,vitamin A and CRS.The pharmacological functions and therapeutic pathways of the genes were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.The candidate naturally bioactive compounds against the key genes were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The anti-inflammatory activity of luteolin was assessed by real-time polymerase chain reaction.RESULTS:Among the 20 co-targeted genes of glucocorticoids,chloroquine and vitamin A,interleukin 10(IL-10),interleukin 2(IL-2),interleukin 4(IL-4)and tumor necrosis factor-α(TNF-α)were the key cytokines against CRS.The key pathway involved in the pharmacological mechanism could be cytokine-cytokine receptor interaction pathway,T cell receptor signaling pathway,Janus Kinase-signal transducer and activator of transcription signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling pathway.Luteolin targeted by IL-10,IL-4,IL-2 and TNF-αcould be one candidate drug for the treatment of CRS.CONCLUSION:This study comprehensively elucidates the pharmacological mechanism for the treatment of CRS and provides a new method for the discovery of drugs for this disease.展开更多
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
基金supported by the Henan Medical Science and Technology Joint Building Program(No.LHGJ20230283)the Medical Science and Technology Research Project of Henan Province(No.SBGJ202103079).
文摘Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2020YFA0707704)the National Key Research and Development Program of China(Grant No.2016YFC1303800)+1 种基金the Jilin Scientific and Technological Development Program(CN)(Grant No.20190303146SF)the National Natural Science Foundation of China(Grant No.81874052).
文摘Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.
基金Supported by National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Building Project for Major Diseases(Lung Cancer)National Key R&D Program of China,No.2016YFC1303300Xiangya Clinical Big Data Project of Central South University(Clinical big data project of lung cancer).
文摘BACKGROUND Cytokine release syndrome(CRS)is defined as systemic inflammation that usually occurs following chimeric antigen receptor T-cell therapy administration;however,it has not been reported in patients with untreated non-small cell lung cancer to date.CASE SUMMARY A 44-year-old nonsmoking woman presented to the hospital due to fever,palpitation,nausea,and cough for 1 mo and was diagnosed with stage cT3N3M0(IIIc)adenocarcinoma of the lung.Auxiliary examinations revealed elevated cytokine[tumor necrosis factor-α,interleukin(IL)-1β,and IL-6]and inflammatory factor levels,which decreased after treatment with corticosteroids and immunoglobulin and when tumor growth was controlled following chemotherapy,radiotherapy,and antiangiogenesis therapy.However,tumor recurrence was observed.After administration of nivolumab as third-line treatment,the patient’s condition was transiently controlled;however,CRS-like symptoms suddenly emerged,which led to a resurgence of cytokines and inflammatory factors and rapid death.CONCLUSION CRS can develop in treatment-naïve lung cancer patients.Patients with tumorrelated CRS may be at risk of CRS recurrence,aggravation,and onset of immune checkpoint inhibitor-related adverse events.
文摘BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis(RM)followed by CART therapy treatment has not been previously reported.CASE SUMMARY We report a case of a 22-year-old woman with relapsed acute lymphoblastic leukemia obtained sequential cluster of differentiation(CD)19 and CD22 CAR-T infusion.This patient experienced grade 3 CRS with RM,mild hypotension requiring intravenous fluids,and mild hypoxia and was managed effectively with the IL-6 receptor antagonist tocilizumab.This patient had no signs of immune effector cell-associated neurologic syndrome.Restaging scans 30 d postCAR-T therapy demonstrated a complete remission,and the symptoms of muscle weakness improved through rehabilitation.CONCLUSION Myalgia is an easily overlooked symptom of severe CRS after CAR-T therapy.It is necessary to monitor myoglobin levels when a patient presents with symptoms of myalgia or acute renal insufficiency.
基金Supported by Weifang Health Commission's Scientific Research Program,No.WFWSJK-2023-222 and No.WFWSJK-2023-240the Weifang Young Medical Talent Support Project.
文摘Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine in recent years.ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic.In order to achieve early clinical prediction and management of immune-related adverse events(irAEs),it is still necessary to perform further research on the mechanisms,risk factors,and predictors of irAE occurrence in the future.Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis.This case provides an important reference for the use of programmed cell death protein-1(PD-1)inhibitors in patients of tumours combined with chronic plaque psoriasis.This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours.PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immunerelated adverse events such as toxic epidermal necrolysis release and psoriasis.Glucocorticosteroids are the first-line agents for irAEs.The incidence of rheumatic irAEs may be higher in reality,which will inevitably become a new challenge for rheumatologists and dermatologists.
文摘Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
基金National Natural Science Foundation of China(81900176,81730008,81870080,and 91949115)National Key R&D Program of China,Stem Cell and Translation Research(2018YFA0109300)+1 种基金Zhejiang Provincial Key Research and Development Program(2018C03016-2,2019C03016)Zhejiang Province Science Foundation for Distinguished Young Scholars(LR19H080001).
文摘Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune diseases.Particularly,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ dysfunction.However,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the host.Although a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear.In the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS.Considering that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.
文摘Since the publication of this review1,the authors noticed one inadvertent mistake occurred in Fig.6c that needs to be corrected.The correct Fig.6 is provided as follows.In detail,"Human-derived CAR-T cells"has been replaced by"Mouse-derived CAR-T cells"in the revised fig.6c.The key findings of the article are not affected by these corrections.The original review article has been corrected.
基金Supported by the“Double-First Class”project of Beijing(No.1000041510155)。
文摘OBJECTIVE:To verify the efficacy of glucocorticoids,chloroquine and vitamin A in the treatment of cytokine release syndrome(CRS),and to investigate the underlying mechanisms,based on network pharmacology.METHODS:We used network pharmacology analysis and found 20 co-targeted genes of glucocorticoids,chloroquine,vitamin A and CRS.The pharmacological functions and therapeutic pathways of the genes were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.The candidate naturally bioactive compounds against the key genes were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The anti-inflammatory activity of luteolin was assessed by real-time polymerase chain reaction.RESULTS:Among the 20 co-targeted genes of glucocorticoids,chloroquine and vitamin A,interleukin 10(IL-10),interleukin 2(IL-2),interleukin 4(IL-4)and tumor necrosis factor-α(TNF-α)were the key cytokines against CRS.The key pathway involved in the pharmacological mechanism could be cytokine-cytokine receptor interaction pathway,T cell receptor signaling pathway,Janus Kinase-signal transducer and activator of transcription signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling pathway.Luteolin targeted by IL-10,IL-4,IL-2 and TNF-αcould be one candidate drug for the treatment of CRS.CONCLUSION:This study comprehensively elucidates the pharmacological mechanism for the treatment of CRS and provides a new method for the discovery of drugs for this disease.
