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
Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most st...Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.展开更多
An artificial immune system was modelled with self/non-self selection to overcome abnormity in a mobile robot demo. The immune modelling includes the innate immune modelling and the adaptive immune modelling. The self...An artificial immune system was modelled with self/non-self selection to overcome abnormity in a mobile robot demo. The immune modelling includes the innate immune modelling and the adaptive immune modelling. The self/non-self selection includes detection and recognition, and the self/non-self detection is based on the normal model of the demo. After the detection, the non-self recognition is based on learning unknown non-self for the adaptive immunization. The learning was designed on the neural network or on the learning mechanism from examples. The last step is elimination of all the non-self and failover of the demo. The immunization of the mobile robot demo is programmed with Java to test effectiveness of the approach. Some worms infected the mobile robot demo, and caused the abnormity. The results of the immunization simulations show that the immune program can detect 100% worms, recognize all known Worms and most unknown worms, and eliminate the worms. Moreover, the damaged files of the mobile robot demo can all be repaired through the normal model and immunization. Therefore, the immune modelling of the mobile robot demo is effective and programmable in some anti-worms and abnormity detection applications.展开更多
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.
基金supported by a Stand Up To Cancer-American Cancer Society Dream Team Translation Research Grant
文摘Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.
基金Projects(60234030, 60404021) supported by the National Natural Science Foundation of China project(040125) supported by the Doctoral Research Grant of Central South University
文摘An artificial immune system was modelled with self/non-self selection to overcome abnormity in a mobile robot demo. The immune modelling includes the innate immune modelling and the adaptive immune modelling. The self/non-self selection includes detection and recognition, and the self/non-self detection is based on the normal model of the demo. After the detection, the non-self recognition is based on learning unknown non-self for the adaptive immunization. The learning was designed on the neural network or on the learning mechanism from examples. The last step is elimination of all the non-self and failover of the demo. The immunization of the mobile robot demo is programmed with Java to test effectiveness of the approach. Some worms infected the mobile robot demo, and caused the abnormity. The results of the immunization simulations show that the immune program can detect 100% worms, recognize all known Worms and most unknown worms, and eliminate the worms. Moreover, the damaged files of the mobile robot demo can all be repaired through the normal model and immunization. Therefore, the immune modelling of the mobile robot demo is effective and programmable in some anti-worms and abnormity detection applications.
