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Complex interplay between tumor microenvironment and cancer therapy

Minhong Shen, Yibin Kang

Frontiers of Medicine 2018, Volume 12, Issue 4,   Pages 426-439 doi: 10.1007/s11684-018-0663-7

Abstract:

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within

Keywords： tumor microenvironment     therapy response     treatment resistance    

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Nanovaccines for remodeling the suppressive tumor microenvironment: New horizons in cancer immunotherapy

Kai Shi, Matthew Haynes, Leaf Huang

Frontiers of Chemical Science and Engineering 2017, Volume 11, Issue 4,   Pages 676-684 doi: 10.1007/s11705-017-1640-4

Abstract: Specifically, reversing the immune-suppressive effects of the tumor microenvironment, mediated by a variety

Keywords： vaccine     nanoparticle     tumor     immunotherapy     microenvironment    

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Heterogeneity of the tumor immune microenvironment and clinical interventions

Frontiers of Medicine 2023, Volume 17, Issue 4,   Pages 617-648 doi: 10.1007/s11684-023-1015-9

Abstract: Heterogeneity of the tumor immune microenvironment and clinical interventions

Keywords： Heterogeneity tumor immune    

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Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma

Frontiers of Medicine 2023, Volume 17, Issue 4,   Pages 699-713 doi: 10.1007/s11684-022-0972-8

Abstract: 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.

Keywords： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment    

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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

Frontiers of Medicine doi: 10.1007/s11684-023-1017-7

Abstract: The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS3) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

Keywords： single-cell RNA-seq     glioma     radial glia     primitive oligodendrocyte precursor cell     immune escape    

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Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

Frontiers of Medicine 2021, Volume 15, Issue 4,   Pages 551-561 doi: 10.1007/s11684-020-0760-2

Abstract: ., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrierSeveral studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment.introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment

Keywords： glioma     evolution mechanism     strategies     tumor heterogeneity     secondary glioma    

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Immunometabolism: a new dimension in immunotherapy resistance

Frontiers of Medicine 2023, Volume 17, Issue 4,   Pages 585-616 doi: 10.1007/s11684-023-1012-z

Abstract: Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

Keywords： immune cell     immunometabolism     metabolic reprogramming     immunotherapy     resistance     tumor microenvironment    

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Translational medicine in hepatocellular carcinoma

Qiang Gao, Yinghong Shi, Xiaoying Wang, Jian Zhou, Shuangjian Qiu, Jia Fan

Frontiers of Medicine 2012, Volume 6, Issue 2,   Pages 122-133 doi: 10.1007/s11684-012-0193-7

Abstract: As a typical virus and inflammation-associated cancer, both host immune response and tumor microenvironmentwe examine the potential of immunotherapy and strategies targeting various components of the tumor microenvironment

Keywords： hepatocellular carcinoma     molecular classification     molecular targeted therapies     tumor microenvironment    

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Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Frontiers of Chemical Science and Engineering 2022, Volume 16, Issue 3,   Pages 333-344 doi: 10.1007/s11705-021-2059-5

Abstract: therapeutic principle, we further discussed the tumor type-specific complexity in the immunological tumor microenvironment

Keywords： nano-enabled hyperthermia     immunogenic cell death     heterogeneous immunological landscape     tumor microenvironment    

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Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke

Frontiers of Medicine 2022, Volume 16, Issue 3,   Pages 429-441 doi: 10.1007/s11684-021-0842-9

Abstract: The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporalchanges of the microenvironment in the pathological process provide vital clues for understanding the

Keywords： ischemic stroke     microenvironment     induced pluripotent stem cells (iPSCs)     positron emission tomography    

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4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine tumor

Hui QIU, Hui ZHANG, Zuohua FENG

Frontiers of Medicine 2009, Volume 3, Issue 1,   Pages 20-25 doi: 10.1007/s11684-009-0006-9

Abstract: These findings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance

Keywords： 4-1BB ligand     tumor immunotherapy     tumor microenvironment    

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Microenvironmental time-activity patterns in Chongqing, China

Yu ZHAO, Shuxiao WANG, Gangcai CHEN, Fei WANG, Kristin AUNAN, Jiming HAO

Frontiers of Environmental Science & Engineering 2009, Volume 3, Issue 2,   Pages 200-209 doi: 10.1007/s11783-009-0010-y

Abstract: An investigation using recall questionnaires was conducted in winter and autumn 2006 to evaluate the time-activity patterns in Chongqing, China. The average time spent in seven microenvironments (MEs) including outdoors, transit, living room, bedroom, kitchen, classroom/office, and other indoors were found to be about 3.5, 1.1, 2.5, 9.7, 1.4, 4.2, and 1.7 h per day, respectively. According to the results of a nonparametric test, the sampling period and day of week were significant for the variation of the time spent in all MEs except for transit and outdoors. The time budget was analyzed using a general linear model (GLM), which exhibited significant variability by demographic factors such as gender, age, residence, education, and household income.

Keywords： time-activity patterns     microenvironment     general linear model (GLM)     Chongqing     China    

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The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

Frontiers of Medicine 2021, Volume 15, Issue 3,   Pages 495-505 doi: 10.1007/s11684-020-0790-9

Abstract: On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of “traditional Chinese medicine (TCM) regulating liver regeneration.” A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of “TCM regulating liver regeneration” (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups ( <0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.

Keywords： hepatitis B virus-related liver failure     traditional Chinese medicine     liver regeneration     liver regeneration microenvironment    

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Nanotechnology: A New Strategy for Lung Cancer Treatment Targeting Pro-Tumor Neutrophils Review

Jian Zhang, Shasha Jiang, Shilin Li, Jipeng Jiang, Jie Mei, Yandong Chen, Yongfu Ma, Yang Liu, Ying Liu

Engineering 2023, Volume 27, Issue 8,   Pages 106-126 doi: 10.1016/j.eng.2022.11.006

Abstract: Tumor development and progression involve communication between tumor cells and the host microenvironmentNeutrophils are the most abundant immune cells in the tumor microenvironment (TME); they participate

Keywords： Lung cancer     Metastasis     Neutrophils     Tumor microenvironment     Nanotechnology    

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Title Author Date Type Operation

Complex interplay between tumor microenvironment and cancer therapy

Minhong Shen, Yibin Kang

Journal Article

Nanovaccines for remodeling the suppressive tumor microenvironment: New horizons in cancer immunotherapy

Kai Shi, Matthew Haynes, Leaf Huang

Journal Article

Heterogeneity of the tumor immune microenvironment and clinical interventions

Journal Article

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma

Journal Article

Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

Journal Article

Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

Journal Article

Immunometabolism: a new dimension in immunotherapy resistance

Journal Article

Translational medicine in hepatocellular carcinoma

Qiang Gao, Yinghong Shi, Xiaoying Wang, Jian Zhou, Shuangjian Qiu, Jia Fan

Journal Article

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Journal Article

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke

Journal Article

4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine tumor

Hui QIU, Hui ZHANG, Zuohua FENG

Journal Article

Microenvironmental time-activity patterns in Chongqing, China

Yu ZHAO, Shuxiao WANG, Gangcai CHEN, Fei WANG, Kristin AUNAN, Jiming HAO

Journal Article

The “Traditional Chinese medicine regulating liver regeneration” treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data

Ling Dai, Xiang Gao, Zhihua Ye, Hanmin Li, Xin Yao, Dingbo Lu, Na Wu

Journal Article

Nanotechnology: A New Strategy for Lung Cancer Treatment Targeting Pro-Tumor Neutrophils

Jian Zhang, Shasha Jiang, Shilin Li, Jipeng Jiang, Jie Mei, Yandong Chen, Yongfu Ma, Yang Liu, Ying Liu

Journal Article

Li Xiaonian: Bionic Strategy to Build Catalytic Reaction Microenvironment (2019.5.24)

22 Apr 2021

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