细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)是一种白细胞分化抗原,也是T细胞上的一种跨膜受体,目前针对CTLA-4在抑制T细胞免疫应答中所起作用的研究取得了一定的突破和成绩,与程序性死亡受体1(p...细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)是一种白细胞分化抗原,也是T细胞上的一种跨膜受体,目前针对CTLA-4在抑制T细胞免疫应答中所起作用的研究取得了一定的突破和成绩,与程序性死亡受体1(programmed death receptor-1,PD-1)共同打开了肿瘤治疗的新局面。通过对上述两个靶点的抑制,可以激活免疫系统,增强T细胞介导的免疫反应,从而增强患者的抗肿瘤能力,并且相应的免疫检查点抑制剂(例如抗CTLA-4单克隆抗体Ipilimumab)已用于黑色素瘤、肺癌等癌种的临床治疗。现就CTLA-4、抗CTLA-4单克隆抗体在肺癌中的作用机制及研究进展作一综述。展开更多
Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction ...Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.展开更多
Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im...Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.展开更多
There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-sma...There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.展开更多
OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Pos...OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Possible molecular mechanisms of differentiation and metastasis of NSCLCs are discussed. METHODS Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA in 68 primary NSCLCs cases. RESULTS The E-cad expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.E-cad expression had a positive correlation with the histological- differentiated grade.A significant difference of E-cad expression was found between metastatic and non-metastatic groups.PCNA expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.The PCNA expression had a reverse correlation with the histological-differentiated grade.A significant difference of PCNA expression was found between metastatic and non-metastatic groups.The E-cad and PCNA expression presented a reverse correlation. CONCLUSION E-cad expression is not associated with the histological type of NSCLC,but is associated with differentiation and metastasis of the cancer.Down-regulation of E-cad expression affects the proliferation of cancer cells.Conjoint analysis of E-cad and PCNA expression is a good way to evaluate tumor biological behavior.展开更多
Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve c...Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital （the Affiliated Hospital of Medical College Qingdao University, China） were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group （D1 ＋ D2） and control group （D1）. The control group （D1） only received radiotherapy to the chest; combined treatment group （D1 ＋ D2） received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results： There was no significant difference in the ratio between two groups in cells CD4＋, CD8＋ and CD4＋/CD8＋ after radiotherapy （P 〉 0.05）. There was no change in these indicators in combined treatment group after treatment （P 〉 0.05）, but it decreased in control group （P 〈 0.05）. There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups （P 〉 0.05）, but the patients in combined treatment group seemed to tolerate high dose well （P 〈 0.05）. Conclusion： Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient＇s immune function.展开更多
文摘细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)是一种白细胞分化抗原,也是T细胞上的一种跨膜受体,目前针对CTLA-4在抑制T细胞免疫应答中所起作用的研究取得了一定的突破和成绩,与程序性死亡受体1(programmed death receptor-1,PD-1)共同打开了肿瘤治疗的新局面。通过对上述两个靶点的抑制,可以激活免疫系统,增强T细胞介导的免疫反应,从而增强患者的抗肿瘤能力,并且相应的免疫检查点抑制剂(例如抗CTLA-4单克隆抗体Ipilimumab)已用于黑色素瘤、肺癌等癌种的临床治疗。现就CTLA-4、抗CTLA-4单克隆抗体在肺癌中的作用机制及研究进展作一综述。
文摘Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.
文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.
文摘There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.
文摘OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Possible molecular mechanisms of differentiation and metastasis of NSCLCs are discussed. METHODS Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA in 68 primary NSCLCs cases. RESULTS The E-cad expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.E-cad expression had a positive correlation with the histological- differentiated grade.A significant difference of E-cad expression was found between metastatic and non-metastatic groups.PCNA expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.The PCNA expression had a reverse correlation with the histological-differentiated grade.A significant difference of PCNA expression was found between metastatic and non-metastatic groups.The E-cad and PCNA expression presented a reverse correlation. CONCLUSION E-cad expression is not associated with the histological type of NSCLC,but is associated with differentiation and metastasis of the cancer.Down-regulation of E-cad expression affects the proliferation of cancer cells.Conjoint analysis of E-cad and PCNA expression is a good way to evaluate tumor biological behavior.
文摘Objective： The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer （NSCLC）. Methods： Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital （the Affiliated Hospital of Medical College Qingdao University, China） were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group （D1 ＋ D2） and control group （D1）. The control group （D1） only received radiotherapy to the chest; combined treatment group （D1 ＋ D2） received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results： There was no significant difference in the ratio between two groups in cells CD4＋, CD8＋ and CD4＋/CD8＋ after radiotherapy （P 〉 0.05）. There was no change in these indicators in combined treatment group after treatment （P 〉 0.05）, but it decreased in control group （P 〈 0.05）. There was no significant difference in the incidences of radiation esophagitis, pneumonia, gastrointestinal reactions and bone marrow suppression between two groups （P 〉 0.05）, but the patients in combined treatment group seemed to tolerate high dose well （P 〈 0.05）. Conclusion： Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient＇s immune function.
