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
目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。...目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。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.
文摘目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。
