Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advance...Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.展开更多
The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the...The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.展开更多
BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis aft...BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy.CASE SUMMARY Both case 1 and case 2 presented with common symptoms of fatigue,nausea,and vomiting.However,case 3 showed rare acute severe symptoms such as hoarse voice,bucking,and difficulty in breathing even when sitting.Following two cycles of immunotherapy in case 3,the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis.These symptoms were relieved after 10 d of steroid treatment.Case 3 was the first patient with these specific symptoms,which provided a new insight into the diagnosis of hypophysitis.In addition,we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy.Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment.Cases 1 and 2 were treated with the low-dose hormone,and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment.CONCLUSION The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.展开更多
This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart...This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The fact...BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.展开更多
基金Natural Science Foundation of Gansu Province,No.21JR1RA186and the Health Industry Research Program of Gansu Province,No.GSWSKY2021-043.
文摘Despite the continuous developments and advancements in the treatment of gastric cancer(GC),which is one of the most prevalent types of cancer in China,the overall survival is still poor for most patients with advanced GC.In recent years,with the progress in tumor immunology research,attention has shifted toward immunotherapy as a therapeutic approach for GC.Programmed cell death protein 1(PD-1)inhibitors,as novel immunosuppressive medications,have been widely utilized in the treatment of GC.However,many patients are still resistant to PD-1 inhibitors and experience recurrence in the advanced stages of PD-1 immunotherapy.To reduce the occurrence of drug resistance and recurrence in GC patients receiving PD-1 immunotherapy,to maximize the clinical activity of immunosuppressive drugs,and to elicit a lasting immune response,it is essential to research the tumor microenvironment mechanisms leading to PD-1 inhibitor resistance in GC patients.This article reviews the progress in studying the factors influencing the resistance to PD-1 inhibitors in the GC tumor microenvironment,aiming to provide insights and a basis for reducing resistance to PD-1 inhibitors for GC patients in the future.
文摘The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.
文摘BACKGROUND Hypophysitis induced by programmed cell death 1 protein(PD-1)immune checkpoint inhibitors is rare and poorly described.We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy.CASE SUMMARY Both case 1 and case 2 presented with common symptoms of fatigue,nausea,and vomiting.However,case 3 showed rare acute severe symptoms such as hoarse voice,bucking,and difficulty in breathing even when sitting.Following two cycles of immunotherapy in case 3,the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis.These symptoms were relieved after 10 d of steroid treatment.Case 3 was the first patient with these specific symptoms,which provided a new insight into the diagnosis of hypophysitis.In addition,we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy.Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment.Cases 1 and 2 were treated with the low-dose hormone,and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment.CONCLUSION The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.
文摘This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.
基金Supported by The 13^(th)Five-Year Plan of Ministry of Science and Technology of the People’s Republic of China,No.2017ZX10302201-004-009,and No.2017ZX10203202-003Beijing Municipal Science and Technology Commission of Major Projects,No.D161100002716002,and No.D161100002716003.
文摘BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.
