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 melanomabearing 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 immuno-therapy.This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy,pre-venting tumor recurrence or metastasis after surgery by rebuilding the patients’immunity,thus consolidating the overall prognosis.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。
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 melanomabearing 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 immuno-therapy.This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy,pre-venting tumor recurrence or metastasis after surgery by rebuilding the patients’immunity,thus consolidating the overall prognosis.
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。
