Tumor Microenvironment and its Implications for Antitumor Immunity in Cholangiocarcinoma: Future Perspectives for Novel Therapies

Cao, Hengsong; Huang, Tian; Dai, Mingrui; Kong, Xiangyi; Liu, Hanyuan; Zheng, Zhihong; Sun, Guoqiang; Sun, Guangshun; Ding, Rong; Jin, Zhong; Tang, Weiwei; Xia, Yongxiang

doi:10.7150/ijbs.73949

Cited by 15 publications

(13 citation statements)

References 165 publications

(128 reference statements)

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“…There are two types of macrophages: M1 (anti-tumor activity) ( 106 , 107 ) and M2 (pro-tumor activity) ( 108 ). Generally, TAMs mainly refer to M2 macrophages, which are characterized by high expression of arginase1 (Arg1), chitinase-like 3 (Ym1/Chil3), found in inflammatory zone 1 (Fizz1) and mannose receptor (MR) ( 109 , 110 ).…”

Section: Regulation Of Irf4 In Immunosuppressive Cells In the Tmementioning

confidence: 99%

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Liang²,

Li³

et al. 2023

Front. Immunol.

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The tumor microenvironment (TME) is implicated in tumorigenesis, chemoresistance, immunotherapy failure and tumor recurrence. Multiple immunosuppressive cells and soluble secreted cytokines together drive and accelerate TME disorders, T cell immunodeficiency and tumor growth. Thus, it is essential to comprehensively understand the TME status, immune cells involved and key transcriptional factors, and extend this knowledge to therapies that target dysfunctional T cells in the TME. Interferon regulatory factor 4 (IRF4) is a unique IRF family member that is not regulated by interferons, instead, is mainly induced upon T-cell receptor signaling, Toll-like receptors and tumor necrosis factor receptors. IRF4 is largely restricted to immune cells and plays critical roles in the differentiation and function of effector cells and immunosuppressive cells, particularly during clonal expansion and the effector function of T cells. However, in a specific biological context, it is also involved in the transcriptional process of T cell exhaustion with its binding partners. Given the multiple effects of IRF4 on immune cells, especially T cells, manipulating IRF4 may be an important therapeutic target for reversing T cell exhaustion and TME disorders, thus promoting anti-tumor immunity. This study reviews the regulatory effects of IRF4 on various immune cells in the TME, and reveals its potential mechanisms, providing a novel direction for clinical immune intervention.

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Section: Regulation Of Irf4 In Immunosuppressive Cells In the Tmementioning

confidence: 99%

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Liang²,

Li³

et al. 2023

Front. Immunol.

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“…The tumor microenvironment is complex. In addition to the diversity of tumor cells, the immune system is another significant category [ 57 ]. The tumor immune microenvironment mediates the phenotypic polarization of the immune cells and stimulates tumor development.…”

Section: Dual Significance Of T-mps In Immune System Regulationmentioning

confidence: 99%

Challenges and Opportunities for Extracellular Vesicles in Clinical Oncology Therapy

Cui

et al. 2023

Bioengineering

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Extracellular vesicles (EVs) are membrane-bound vesicles that can be released by all cell types. They may have different biogenesis, physical features, and cargo. EVs are important biomarkers for the diagnosis and prediction of many diseases due to their essential role in intercellular communication, their highly variable cargoes, and their accumulation in various body fluids. These natural particles have been investigated as potential therapeutic materials for many diseases. In our previous studies, the clinical usage of tumor-cell-derived microparticles (T-MPs) as a novel medication delivery system was examined. This review summarizes the clinical translation of EVs and related clinical trials, aiming to provide suggestions for safer and more effective oncology therapeutic systems, particularly in biotherapeutic and immunotherapeutic systems.

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“…The TME is a cellular niche comprising a dynamic heterogeneous collection of tumor or cancer stem cells, as well as being involved in the constant modulation of infiltrating and resident host cells, secretory factors, and ECM ( Xiao and Yu, 2021 ). This niche not only includes the structure, function and metabolism of the tumor-host tissue, but also the internal environment (nucleus and cytoplasm) of the tumor cells themselves ( Anderson and Simon, 2020 ; Cao et al, 2022 ). The cellular components of the TME include the tumor cells themselves, as well as adipocytes, fibroblasts, tumor vascular system, lymphocytes, dendritic cells, and tumor-related fibroblasts ( Figure 2 ), each of which has a unique immune capacity that will determine the survivability and influence of tumor cells on neighboring cells ( Arneth, 2019 ).…”

Section: The Tmementioning

confidence: 99%

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment

Zhou

Duan

et al. 2022

Front. Pharmacol.

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It is well known that tumor cells rely mainly on aerobic glycolysis for energy production even in the presence of oxygen, and glycolysis is a known modulator of tumorigenesis and tumor development. The tumor microenvironment (TME) is composed of tumor cells, various immune cells, cytokines, and extracellular matrix, among other factors, and is a complex niche supporting the survival and development of tumor cells and through which they interact and co-evolve with other tumor cells. In recent years, there has been a renewed interest in glycolysis and the TME. Many studies have found that glycolysis promotes tumor growth, metastasis, and chemoresistance, as well as inhibiting the apoptosis of tumor cells. In addition, lactic acid, a metabolite of glycolysis, can also accumulate in the TME, leading to reduced extracellular pH and immunosuppression, and affecting the TME. This review discusses the significance of glycolysis in tumor development, its association with the TME, and potential glycolysis-targeted therapies, to provide new ideas for the clinical treatment of tumors.

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Tumor Microenvironment and its Implications for Antitumor Immunity in Cholangiocarcinoma: Future Perspectives for Novel Therapies

Cited by 15 publications

References 165 publications

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Challenges and Opportunities for Extracellular Vesicles in Clinical Oncology Therapy

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment

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