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Evolving strategies for tumor immunotherapy:enhancing the enhancer and suppressing the suppressor

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National Science Review 2017年第2期4卷 161-163页

作者： Yan Gu Yanfang Liu Xuetao Cao National Key laboratory of Medical immunology & Institute of immunology Second Military Medical University Department of Pathology Changhai HospitalSecond Military Medical University Department of immunology & Center for immunotherapy Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical Sciences

Cancers develop complex and dynamic tissue microenvironments to support their sustained growth,invasion and *** decades,rapid progress has been made in the cross talk between tumor cells and the surrounding microenvir... 详细信息

关键词： cell MDSC Evolving strategies for tumor immunotherapy:enhancing the enhancer and suppressing the suppressor

cGAS-STING pathway in senescence-related inflammation

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National Science Review 2018年第3期5卷 308-310页

作者： Kun Chen Juan Liu Xuetao Cao National Key laboratory of Medical Molecular Biology Department of Immunology & Center for Immunotherapy Institute of Basic Medical Sciences Peking Union Medical College Chinese Academy of Medical Sciences National Key laboratory of Medical immunology & Institute of immunology Second Military Medical University

Cellular senescence marked with persistent cell cycle arrest plays critical roles in orchestrating tissue remodeling and immune surveillance in response to multiple developmental and physiological ***,chronic or persistent cellular senescence can promote aberrant inflammatory responses,therefore is linked with variable pathogeneses such as fibrosis,cancer,autoimmune diseases,

关键词： GAS cGAS-STING pathway in senescence-related inflammation

Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 492-502页

作者： Anil Suri Nirmala Jagadish Shikha Saini Namita Gupta Cancer Microarray Genes and Proteins Laboratory National Institute of Immunology

Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

关键词： Cancer testis antigens Colorectal cancer Testis sp

Natural Killer Cell-Based immunotherapy for Cancer: Advances and Prospects

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Engineering 2019年第1期5卷 106-114页

作者： Yuan Hu Zhigang Tian Cai Zhang Institute of Immunopharmacology and immunotherapy School of Pharmaceutical Sciences Shandong University Jinan 250012 China Institute of immunology School of Life Sciences University of Science and Technology of China Hefei 230061 China

Natural killer (NK) cells are key innate immune cells that provide the first line of defense against viral infection and cancer. Although NK cells can discriminate between "self" and "non-self," recognize abnormal cells, and eliminate transformed cells and malignancies in real time, tumors develop several strategies to escape from NK cell attack. These strategies include upregulating ligands for the inhibitory receptors of NK cells and producing soluble molecules or immunosuppressive factors. Various types of NK cells are currently being applied in clinical trials, including autologous or allogeneic NK cells, umbilical cord blood (UCB) or induced pluripotent stem cell (iPSC)-derived NK cells, memory-like NK cells, and NK cell line NK-92 cells, for the treatment of different types of tumors. Chimeric antigen receptors (CARs)-NK cells have recently shown great potential due to their redirect specificity and effective antitumor activity. In this review, we summarize the mechanisms of tumor escape from NK cell recognition, the current status and advanced progress of NK cell-based immunotherapy, ways of enhancing the antitumor capacity of NK cells in vivo, and major challenges for clinical practice in this field.

关键词： Natural killer cell immunotherapy Cancer Clinical trial Chimeric antigen receptor

Chimeric antigen receptor engineered innate immune cells in cancer immunotherapy

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Science China(Life Sciences) 2019年第5期62卷 633-639页

作者： Chu Lin Jun Zhang Department of immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology (Peking University) Peking University Health Science Center

Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cells first caught researchers' attention and became great success in chimeric antigen receptor-based immunotherapy. However, engineered T cells seem to hit their bottleneck when resistance of cancerous cells, less encouraging responses in solid tumors and unwanted toxicities to the host remain to be ***, innate immune cells get to join the race. Representatives such as natural killer cells, natural killer T cells, γδT cells and macrophages also prove to be well redirected with chimeric antigen receptors. Compared to chimeric antigen receptor engineered T cells, these engineered innate immune cells may possess multiple targeting and killing mechanisms, have the potential to crack the barrier of solid tumors and have less side effects in the host. Besides, possible universal access to cell resources and improvements in expansion and transduction techniques make these cells promising candidates with huge potential in translational medicine. Therefore, innate immune cells claim a brand-new dimension and are likely to supplement T cells greatly in the field of chimeric antigen receptor-based immunotherapy.

关键词： chimeric antigen receptor cancer immunotherapy innate immune cell

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Reversing the mitochondrial stress-induced exhaustion of CD8^(+)T cells for improving cancer immunotherapy

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Cellular & Molecular immunology 2021年第7期18卷 1634-1637页

作者： Cheng Qian Xuetao Cao National Key laboratory of Medical immunology Institute of ImmunologySecond Military Medical UniversityShanghaiChina laboratory of Immunity and Inflammation College of Life SciencesNankai UniversityTianjinChina

Antigen-specific CD8+T cells that infiltrate tumor tissue have been considered the primary cytotoxic lymphocytes that exert antitumor effects,building a foundation for current immunotherapies against ***,in the face of continuous antigenic stimulation during chronic infections and cancer,T-cell differentiation leads to a state of incapacitation called T-cell exhaustion,which is a critical barrier to successful T-cell immunotherapy of *** explosive growth of malignant tumor cells accompanied by a dysfunctional vascular system and metabolite competition leads to a stressful tumor microenvironment characterized by low-oxygen tension,acidic interstitial pH,and insufficient *** evidence for the contribution of the tumor microenvironment to the metabolic reprogramming of exhausted CD8+T cells has been increasing,but the response of intratumoral T cells to metabolic stress signals is still not fully *** of a study by Scharping et al.,1 together with other recent evidence,have highlighted that the tumor microenvironment can influence the mitochondrial stress of T cells and drive the trajectory of T-cell differentiation toward *** findings add new perspectives on and insights into the molecular initiators of T-cell exhaustion and the combination of strategies that should be utilized to improve the efficacy of immunotherapy,and these perspectives are discussed in this review.

关键词： immunotherapy cancer stimulation

Dendritic cell migration in inflammation and immunity

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Cellular & Molecular immunology 2021年第11期18卷 2461-2471页

作者： Juan Liu Xiaomin Zhang Yujie Cheng Xuetao Cao National Key laboratory of Medical immunology&Institute of immunology Second Military Medical UniversityShanghaiChina Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijingChina

Dendritic cells(DCs)are the key link between innate immunity and adaptive immunity and play crucial roles in both the promotion of immune defense and the maintenance of immune *** trafficking of distinct DC subsets across lymphoid and nonlymphoid tissues is essential for DC-dependent activation and regulation of inflammation and *** chemotaxis and migration are triggered by interactions between chemokines and their receptors and regulated by multiple intracellular mechanisms,such as protein modification,epigenetic reprogramming,metabolic remodeling,and cytoskeletal rearrangement,in a tissue-specific *** of DC migration may lead to abnormal positioning or activation of DCs,resulting in an imbalance of immune responses and even immune pathologies,including autoimmune responses,infectious diseases,allergic diseases and *** strategies targeting the migration of distinct DC subsets are being explored for the treatment of inflammatory and infectious diseases and the development of novel DC-based *** this review,we will discuss the migratory routes and immunological consequences of distinct DC subsets,the molecular basis and regulatory mechanisms of migratory signaling in DCs,and the association of DC migration with the pathogenesis of autoimmune and infectious diseases.

关键词： dendritic cells cell migration chemokine receptor CCR7 inflammation autoimmune diseases

Natural killer cell lines in tumor immunotherapy

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Frontiers of Medicine 2012年第1期6卷 56-66页

作者： Min Cheng Jian Zhang Wen Jiang Yongyan Chen Zhigang Tian Institute of immunology Hefei National Laboratory for Physical Sciences at Microscale and School of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunopharmacology and immunotherapy School of Pharmaceutical SciencesShandong UniversityJinan 250012China

Natural killer(NK)cells are considered to be critical players in anticancer ***,cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK *** NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches,including activating autologous NK cells,expanding allogeneic NK cells,usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell *** stable allogeneic NK cell line approach is more practical for quality-control and large-scale ***,genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and *** this review,NK cells in tumor immunotherapy are discussed,and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.

关键词： natural killer cell natural killer cell line tumor immunotherapy genetic modification

Programmed polymersomes with spatio-temporal delivery of antigen and dual-adjuvants for efficient dendritic cells-based cancer immunotherapy

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Chinese Chemical Letters 2022年第9期33卷 4179-4184页

作者： Hanyong Wang Xinyu Yang Chunyan Hu Chenlu Huang Hai Wang Dunwan Zhu Linhua Zhang Tianjin Key laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China

Since antigen and adjuvant are rapid clearance in vivo,insufficient delivery to induce dendritic cells(DCs)maturation and cross-presentation,as well as limited migration efficiency of DCs to secondary lymph organs,greatly hinders the development of DCs-based ***,PCL-PEG-PCL polymersomes(PCEP-PS)as antigen and adjuvants delivery nanoplatforms(IMO-PS)were well-designed,which can electrostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release,incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses via different signaling *** IMO-PS significantly improved antigen uptake,promoted DCs maturation and cytokines *** treated with IMO-PS could enhance migration into draining lymphoid nodes,and eventually induced antigen-specific CD8+and CD4+T cell responses and OVA-specific cytotoxic T lymphocyte(CTL)*** vaccination of EG7-OVA tumor-bearing mice by IMO-PS+DCs significantly extended tumor-free time,effectively suppressed tumor growth,and greatly extended median survival *** strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.

关键词： DCs vaccine immunotherapy Imiquimod MPLA DOTAP OVA

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