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
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
In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expresse...In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.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
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 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 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz,No.NC23189.0.
文摘In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.
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.