Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantia...Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.展开更多
Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknow...Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9-dependent mechanism.展开更多
Helper T cell(Th)has been identified as a critical immune cell for regulating immune response since 1980s.The type 2 helper Tcell(Th2),characterized by the production of interleukin-4(IL-4),IL-5 and IL-13,plays a crit...Helper T cell(Th)has been identified as a critical immune cell for regulating immune response since 1980s.The type 2 helper Tcell(Th2),characterized by the production of interleukin-4(IL-4),IL-5 and IL-13,plays a critical role in immune response against helminths invading cutaneous or mucosal sites.It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea.Currently,most studies have shed light on Th2 cell function and behavior in specific diseases,such as asthma and helminthes inflammation,but not on Th2 cell itself and its differentiation.Based on different cytokines and specific behavior in recent research,Th2 cell is also regarded as new subtypes of T cell,such as IL-9 secreting T cell(Th9)and CXCR5+T follicular helper cells.Here,we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.展开更多
基金This work was supported by National Natural Science Foundation of China(81872173,82072959,31870959,and 82102855)Zhejiang Province Natural Science Foundation(LY20H160018,LD21H160002,and LY19H160045).
文摘Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.
基金supported by the National Natural Science Foundation of China (91442109, 31470883, 81270149, 81272591)the National Basic Research Program of China (2012CB518706)
文摘Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9-dependent mechanism.
文摘Helper T cell(Th)has been identified as a critical immune cell for regulating immune response since 1980s.The type 2 helper Tcell(Th2),characterized by the production of interleukin-4(IL-4),IL-5 and IL-13,plays a critical role in immune response against helminths invading cutaneous or mucosal sites.It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea.Currently,most studies have shed light on Th2 cell function and behavior in specific diseases,such as asthma and helminthes inflammation,but not on Th2 cell itself and its differentiation.Based on different cytokines and specific behavior in recent research,Th2 cell is also regarded as new subtypes of T cell,such as IL-9 secreting T cell(Th9)and CXCR5+T follicular helper cells.Here,we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.
