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
Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer(NSCLC), where system...Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer(NSCLC), where systemic cytotoxic chemotherapies still remain the backbone of management, is felt more than ever before. Runway success of immunotherapies such as Ipilimumab for melanoma has brought excitement among oncologists. Immune-based treatments are in various stages of evaluation for NSCLC as well. Immunotherapies using strategies of antigen based or cell based vaccines, and blocking immune checkpoints are of substantial interest. Meaningful clinical responses are yet to be reaped from these new treatment modalities.展开更多
Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to ex...Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.展开更多
Trophic properties of hematopoietic stem cells can influence the malignant growth alternatively to immune control. The annual growth of the body mass by age in adult populations of welfare countries used as the most c...Trophic properties of hematopoietic stem cells can influence the malignant growth alternatively to immune control. The annual growth of the body mass by age in adult populations of welfare countries used as the most common criterion of metabolic and proliferative tissue activity, and these data compared with death’ rate for malignant and somatic diseases in different age-groups of the same countries. The rate of physiologic involution of different cell populations in the lymphoid lineage by age also involved in correlations between the above parameters. A decrease in death rate for cancer and increase it’s for non-malignant diseases found in 60+ populations, which have the lowest physiological temp of renewal of lymphocytes number and mass of the body. The lack of both the thymus gland volume and proliferative activity of naive lymphocytes reduces physiological body mass renewal as well as the cancer death rate but enhances somatic death rate, opposing to anticancer immunity at large. A protumor character of the lymphopoietic system’s relation with malignancy seems more realistic than defending one.展开更多
目的:基于CT影像组学预测实性非小细胞肺癌(non-small cell lung cancer,NSCLC)组织细胞程序性死亡-配体1(programmed death ligand 1,PD-L1)蛋白表达状态的价值。方法:回顾性分析经病理证实为NSCLC且影像学上肿瘤表现为实性的患者116例...目的:基于CT影像组学预测实性非小细胞肺癌(non-small cell lung cancer,NSCLC)组织细胞程序性死亡-配体1(programmed death ligand 1,PD-L1)蛋白表达状态的价值。方法:回顾性分析经病理证实为NSCLC且影像学上肿瘤表现为实性的患者116例,其中鳞癌55例,腺癌61例,分析其临床与影像资料,筛选临床独立预测因子并构建临床模型。将图像导出并对其平扫及动脉期图像进行配准,手动逐层勾画肿瘤的感兴趣区域并提取影像组学特征,经过特征筛选后构建影像组学模型并计算每例患者影像组学评分,将影像组学评分与临床独立预测因子进行联合构建列线图。使用受试者工作特征曲线(receiver operating characteristic curve,ROC)的曲线下面积(area under the curve,AUC)评估模型诊断效能,使用决策分析曲线(decision curve analysis,DCA)评价模型的临床效用,利用DeLong检验评估模型之间差异。此外,按鳞癌和腺癌两种病理分型进行分组并进行亚组分析。结果:空洞和影像组学评分是预测PD-L1表达的临床独立预测因子(空洞有优势比为3.624,影像组学优势比为2.532)。列线图的诊断表现(训练组AUC vs验证组AUC:0.861 vs 0.803)优于影像组学模型(AUC:0.847 vs 0.777)和临床模型(AUC:0.608 vs 0.570)。决策曲线表明,列线图相比与临床模型和影像组学模型具有更高的临床应用价值。亚组分析中,列线图仍然具有很好的诊断效能,且在鳞癌组中的诊断效能优于腺癌组。结论:CT影像组学列线图能够在术前有效的预测实性NSCLC组织PD-L1蛋白表达状态,能够为临床方案选择和术前决策提供帮助。展开更多
目的探讨系统性免疫炎症指数(SII)对晚期非小细胞肺癌患者预后的预测价值。方法自2019年1月至2022年6月,回顾性收集新疆医科大学附属肿瘤医院收治的晚期非小细胞肺癌患者143例,对患者随访1年,观察患者是否发生肿瘤特异性死亡,将患者分...目的探讨系统性免疫炎症指数(SII)对晚期非小细胞肺癌患者预后的预测价值。方法自2019年1月至2022年6月,回顾性收集新疆医科大学附属肿瘤医院收治的晚期非小细胞肺癌患者143例,对患者随访1年,观察患者是否发生肿瘤特异性死亡,将患者分为死亡组(n=67)和对照组(n=76),比较两组患者系统性免疫炎症指数和其他临床特征差异,分析晚期非小细胞肺癌死亡的危险因素,同时分析系统性免疫炎症指数对肿瘤特异性死亡的预测价值。结果与对照组比较,死亡组原发肿瘤最大径增大(5.66±2.53 cm vs.4.79±1.91 cm,P=0.020);SII水平显著增高(522.44±242.98 vs.277.84±100.67,P<0.001);TNM分期为Ⅳ期的患者比例增高(76.12%vs.55.26%,P=0.011);合并胸腔积液的患者比例增高(92.54%vs.68.42%,P<0.001)。SII和原发肿瘤最大径对晚期非小细胞肺癌患者肿瘤特异性死亡均有一定预测价值,曲线下面积分别为0.849(95%可信区间:0.790~0.909,P<0.001)和0.598(95%可信区间:0.503~0.693,P=0.044)。原发肿瘤最大径、胸腔积液和SII是晚期非小细胞肺癌患者肿瘤特异性死亡的独立影响因素(P<0.05)。结论晚期非小细胞肺癌患者系统性炎症指数增高与肿瘤特异性死亡有关,可以作为预后的预测指标。展开更多
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Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer(NSCLC), where systemic cytotoxic chemotherapies still remain the backbone of management, is felt more than ever before. Runway success of immunotherapies such as Ipilimumab for melanoma has brought excitement among oncologists. Immune-based treatments are in various stages of evaluation for NSCLC as well. Immunotherapies using strategies of antigen based or cell based vaccines, and blocking immune checkpoints are of substantial interest. Meaningful clinical responses are yet to be reaped from these new treatment modalities.
基金Fund supported by the Healthcare Technology Plan of Zhejiang Provincial Health Bureau(No.2016KYB292)the Technology Plan of Science and Technology Bureau of Jiaxing,Zhejiang province(No.2016AY23054)~~
文摘Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.
文摘Trophic properties of hematopoietic stem cells can influence the malignant growth alternatively to immune control. The annual growth of the body mass by age in adult populations of welfare countries used as the most common criterion of metabolic and proliferative tissue activity, and these data compared with death’ rate for malignant and somatic diseases in different age-groups of the same countries. The rate of physiologic involution of different cell populations in the lymphoid lineage by age also involved in correlations between the above parameters. A decrease in death rate for cancer and increase it’s for non-malignant diseases found in 60+ populations, which have the lowest physiological temp of renewal of lymphocytes number and mass of the body. The lack of both the thymus gland volume and proliferative activity of naive lymphocytes reduces physiological body mass renewal as well as the cancer death rate but enhances somatic death rate, opposing to anticancer immunity at large. A protumor character of the lymphopoietic system’s relation with malignancy seems more realistic than defending one.
文摘目的:基于CT影像组学预测实性非小细胞肺癌(non-small cell lung cancer,NSCLC)组织细胞程序性死亡-配体1(programmed death ligand 1,PD-L1)蛋白表达状态的价值。方法:回顾性分析经病理证实为NSCLC且影像学上肿瘤表现为实性的患者116例,其中鳞癌55例,腺癌61例,分析其临床与影像资料,筛选临床独立预测因子并构建临床模型。将图像导出并对其平扫及动脉期图像进行配准,手动逐层勾画肿瘤的感兴趣区域并提取影像组学特征,经过特征筛选后构建影像组学模型并计算每例患者影像组学评分,将影像组学评分与临床独立预测因子进行联合构建列线图。使用受试者工作特征曲线(receiver operating characteristic curve,ROC)的曲线下面积(area under the curve,AUC)评估模型诊断效能,使用决策分析曲线(decision curve analysis,DCA)评价模型的临床效用,利用DeLong检验评估模型之间差异。此外,按鳞癌和腺癌两种病理分型进行分组并进行亚组分析。结果:空洞和影像组学评分是预测PD-L1表达的临床独立预测因子(空洞有优势比为3.624,影像组学优势比为2.532)。列线图的诊断表现(训练组AUC vs验证组AUC:0.861 vs 0.803)优于影像组学模型(AUC:0.847 vs 0.777)和临床模型(AUC:0.608 vs 0.570)。决策曲线表明,列线图相比与临床模型和影像组学模型具有更高的临床应用价值。亚组分析中,列线图仍然具有很好的诊断效能,且在鳞癌组中的诊断效能优于腺癌组。结论:CT影像组学列线图能够在术前有效的预测实性NSCLC组织PD-L1蛋白表达状态,能够为临床方案选择和术前决策提供帮助。
文摘目的探讨系统性免疫炎症指数(SII)对晚期非小细胞肺癌患者预后的预测价值。方法自2019年1月至2022年6月,回顾性收集新疆医科大学附属肿瘤医院收治的晚期非小细胞肺癌患者143例,对患者随访1年,观察患者是否发生肿瘤特异性死亡,将患者分为死亡组(n=67)和对照组(n=76),比较两组患者系统性免疫炎症指数和其他临床特征差异,分析晚期非小细胞肺癌死亡的危险因素,同时分析系统性免疫炎症指数对肿瘤特异性死亡的预测价值。结果与对照组比较,死亡组原发肿瘤最大径增大(5.66±2.53 cm vs.4.79±1.91 cm,P=0.020);SII水平显著增高(522.44±242.98 vs.277.84±100.67,P<0.001);TNM分期为Ⅳ期的患者比例增高(76.12%vs.55.26%,P=0.011);合并胸腔积液的患者比例增高(92.54%vs.68.42%,P<0.001)。SII和原发肿瘤最大径对晚期非小细胞肺癌患者肿瘤特异性死亡均有一定预测价值,曲线下面积分别为0.849(95%可信区间:0.790~0.909,P<0.001)和0.598(95%可信区间:0.503~0.693,P=0.044)。原发肿瘤最大径、胸腔积液和SII是晚期非小细胞肺癌患者肿瘤特异性死亡的独立影响因素(P<0.05)。结论晚期非小细胞肺癌患者系统性炎症指数增高与肿瘤特异性死亡有关,可以作为预后的预测指标。
