|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy显示文摘Anti-CD19 chimeric antigen receptor(CAR)-T cell therapy has achieved 40%–50%long-term complete response in relapsed or refractory diffuse large B-cell lymphoma(DLBCL)patients.However,the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation.A multi-center phase I/II trial of anti-CD19 CD28z CAR-T(FKC876,ChiCTR1800019661)was conducted.Among 22 evaluable DLBCL patients,seven achieved complete remission,10 experienced partial remissions,while four had stable disease by day 29.Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients,and compared at different stages of treatment.M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells,leading to CAR-T cell therapy failure and disease progression in DLBCL.Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy,during both cell expansion and disease progression,which could not be altered by infiltrating CAR-T cells.Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments.Thus,our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy. | Zixun Yan Li Li Di Fu Wen Wu Niu Qiao Yaohui Huang Lu Jiang Depei Wu Yu Hu Huilai Zhang Pengpeng Xu Shu Cheng Li Wang Sahin Lacin Muharrem Muftuoglu Weili Zhao | 2023 | Frontiers of Medicine2023，17，4： | 0 |
| 2 | Design and preparation of an ultra-high temperature ceramic by in-situ introduction of Zr_(2)[Al(Si)]_(4)C_(5) into ZrB_(2)-SiC:Investigation on the mechanical properties and oxidation behavior显示文摘Novel ZrB_(2)-matrix composites were designed and prepared by in-situ introducing SiC and Zr_(2)[Al(Si)]_(4)C_(5) simultaneously for the first time.The obtained composites were dense and showed good mechanical properties,especially the strength and toughness,706 MPa and 7.33 MPa·m^(1/2),respectively,coupled with high hardness of 21.3 GPa,and stiffness of 452 GPa.SiC and Zr_(2)[Al(Si)]_(4)C_(5) constituted a reinforcing system with synergistic effects including grain refinement,grain pull-out as well as crack branching,bridging,and deflection.Besides,the oxidation results of the composites showed that the oxidation kinetics followed the parabolic law at 1600℃,and the oxidation rate constants increased with the increase of Zr_(2)[Al(Si)]_(4)C_(5) content.The formation and evolution model of the oxidation structure was also investigated,and the oxide scale of the composite exhibited a three-layer structure. | Lei YU Hui LIU Yaohui FU Weijiang HU Zhefei WANG Quan LIU Bo WEI Jian YANG Tai QIU | 2021 | Journal of Advanced Ceramics2021，10，5： | 0 |
| 3 | Arabidopsis SYP121 acts as an ROP2 effector in the regulation of root hair tip growth显示文摘Tip growth is an extreme form of polarized cell expansion that occurs in all eukaryotic kingdoms to generate highly elongated tubular cells with specialized functions, including fungal hyphae, animal neurons, plant pollen tubes, and root hairs (RHs). RHs are tubular structures that protrude from the root epidermis to facilitate water and nutrient uptake, microbial interactions, and plant anchorage. RH tip growth requires polarized vesicle targeting and active exocytosis at apical growth sites. However, how apical exocytosis is spatially and temporally controlled during tip growth remains elusive. Here, we report that the Qa-Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) SYP121 acts as an effector of Rho of Plants 2 (ROP2), mediating the regulation of RH tip growth. We show that active ROP2 promotes SYP121 targeting to the apical plasma membrane. Moreover, ROP2 directly interacts with SYP121 and promotes the interaction between SYP121 and the R-SNARE VAMP722 to form a SNARE complex, probably by facilitating the release of the Sec1/Munc18 protein SEC11, which suppresses the function of SYP121. Thus, the ROP2-SYP121 pathway facilitates exocytic trafficking during RH tip growth. Our study uncovers a direct link between an ROP GTPase and vesicular trafficking and a new mechanism for the control of apical exocytosis, whereby ROP GTPase signaling spatially regulates SNARE complex assembly and the polar distribution of a Q-SNARE. | Xiankui Cui Shuwei Wang Yaohui Huang Xuening Ding Zirong Wang Lidan Zheng Yujing Bi Fanghui Ge Lei Zhu Ming Yuan Shaul Yalovsky Ying Fu | 2022 | Molecular Plant2022，15，6： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员