Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained ...Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.展开更多
Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of...Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma （HCC） and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4＋CD25^highTreq cells in tumor site of HCC.展开更多
Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have s...Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.展开更多
Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involveme...Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.展开更多
基金This work was supported by grants from the Beijing Advanced Innovation Center for Genomics at Peking University,Key Technologies R&D Program(2016YFC0900100 and 2016YFC0902300)the National Natural Science Foundation of China(31530036 and 91742203).
文摘Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.
文摘Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma （HCC） and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4＋CD25^highTreq cells in tumor site of HCC.
基金supported by funding from the Project Nn10 of Harbin Medical University Cancer Hospital(Grant Number Nn102017-02)National Natural Science Foundation of China(Grant Number 81602323,81872149)+3 种基金Outstanding Youth Project of Heilongjiang Provincial Natural Science Foundation(Grant Number YQ2019H027)Distinguished Young Scholars of Harbin Medical University Cancer Hospital(Grant Number JCQN2018-03)Yong Elite Training Foundation Grant of Harbin Medical University Cancer Hospital(Grant Number JY2016-02)Haiyan Fund Project of Harbin Medical University Cancer Hospital(Grant Number JJQN 2018-10).
文摘Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.
基金supported by The National Natural Science Foundation of China(Grant No.81702972,Grant No.81874204)China Postdoctoral Science Foundation(Grant No.2018M640305,Grant No.2019M660074)+4 种基金The Research Project of the Chinese Society of Neuro-oncology,CACA(Grant No.CSNO-2016-MSD12)Heilongjiang Postdoctoral Science Foundation(Grant No.LBH-Z18103)The Research Project of the Health and Family Planning Commission of Heilongjiang Province(Grant No.2017–201)Postgraduate Research&Practice Innovation Program of Harbin Medical University(Grant No.YJSKYCX2018-94HYD)The Young and middle-aged Science Foundation of Harbin Medical University(Grant No.KYCX2018-08)。
文摘Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.
