程序性死亡分子1(programmed death-1,PD1)及其配体(programmed death ligand,PDL)属于B7家族的共刺激分子,介导免疫反应的负性调节信号,在肿瘤发生、病毒感染以及自身免疫病中都发挥了特异性的调节作用。利用PD1/PDL1信号途径调节机体...程序性死亡分子1(programmed death-1,PD1)及其配体(programmed death ligand,PDL)属于B7家族的共刺激分子,介导免疫反应的负性调节信号,在肿瘤发生、病毒感染以及自身免疫病中都发挥了特异性的调节作用。利用PD1/PDL1信号途径调节机体的免疫应答从而达到免疫治疗的目的,该文就此展开综述。展开更多
Cancer patients by immune checkpoint therapy have achieved long-term remission,with no recurrence of clinical symptoms of cancer for many years.Nevertheless,more than half of cancer patients are not responsive to this...Cancer patients by immune checkpoint therapy have achieved long-term remission,with no recurrence of clinical symptoms of cancer for many years.Nevertheless,more than half of cancer patients are not responsive to this therapy due to immune exhaustion.Here,we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod(PD1-Imi Exo)for boosting response of cancer immune checkpoint blockage therapy.The results showed that PD1-Imi Exo had a vesicular round shape(approximately 139 nm),revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell,and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice.The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8^(+)T cell with cancer cell,displaying a PD1/PDL1 immune checkpoint blockage effect,and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell,exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8^(+)T cell.In conclusion,the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy.This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy,preventing tumor recurrence or metastasis after surgery by rebuilding the patients’immunity,thus consolidating the overall prognosis.展开更多
文摘程序性死亡分子1(programmed death-1,PD1)及其配体(programmed death ligand,PDL)属于B7家族的共刺激分子,介导免疫反应的负性调节信号,在肿瘤发生、病毒感染以及自身免疫病中都发挥了特异性的调节作用。利用PD1/PDL1信号途径调节机体的免疫应答从而达到免疫治疗的目的,该文就此展开综述。
基金supported by the National Natural Science Foundation of China(No.82173752 and No.81874303).
文摘Cancer patients by immune checkpoint therapy have achieved long-term remission,with no recurrence of clinical symptoms of cancer for many years.Nevertheless,more than half of cancer patients are not responsive to this therapy due to immune exhaustion.Here,we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod(PD1-Imi Exo)for boosting response of cancer immune checkpoint blockage therapy.The results showed that PD1-Imi Exo had a vesicular round shape(approximately 139 nm),revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell,and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice.The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8^(+)T cell with cancer cell,displaying a PD1/PDL1 immune checkpoint blockage effect,and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell,exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8^(+)T cell.In conclusion,the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy.This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy,preventing tumor recurrence or metastasis after surgery by rebuilding the patients’immunity,thus consolidating the overall prognosis.
文摘目的分析康莱特注射液在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)化疗中的应用效果。方法选择2021年1月至2022年9月我院收治的53例NSCLC患者,随机分为观察组26例,对照组27例。对照组采用PD1/PDL1免疫抑制剂联合化疗,观察组在此基础上加用康莱特注射液。对比两组治疗后客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、不良反应发生率,比较两组治疗前后血清中肿瘤标志物[糖类抗原(carbohydrate antigen,CA)125、癌胚抗原(carcinoembryonic antigen,CEA)、细胞角蛋白19的可溶性片段(soluble fragment of cytokeratin 19,CYFRA21-1)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)]、免疫功能(T淋巴细胞CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)比值)的变化。结果观察组客观缓解20例(76.90%)高于对照组12例(44.44%),χ^(2)=5.840(P<0.05),观察组较对照组疾病控制[21例(80.69%)vs.16(59.25%)]差异无统计学意义(P>0.05);两组治疗后CA125、CEA、CYFRA21-1、NSE降低,观察组CA125[(16.38±2.57)vs.(18.27±3.49)]U/ml、CEA[(13.23±2.88)vs.(17.48±3.40)]ng/ml、CYFRA21-1[(2.78±0.36)vs.(4.11±0.42)]ng/ml、NSE[(8.04±1.76)vs.(9.16±2.08)]ng/ml低于对照组(P<0.05);观察组治疗后CD4^(+)[(50.38±5.17)vs.(39.23±3.49)]%、CD8^(+)[(30.23±4.42)vs.(27.45±3.69)]%、CD4^(+)/CD8^(+)比值[(1.78±0.56)vs.(1.18±0.27)]高于对照组(P<0.05)。结论NSCLC患者PD1/PDL1免疫抑制剂联合康莱特注射液化疗能有效抑制肿瘤发展,改善免疫功能,减少不良反应,具有临床意义。
