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    Home > Active Ingredient News > Immunology News > Nature: West China Hospital reveals heterogeneity and plasticity of cancer-associated fibroblasts

    Nature: West China Hospital reveals heterogeneity and plasticity of cancer-associated fibroblasts

    • Last Update: 2022-11-14
    • Source: Internet
    • Author: User
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    Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment (TME) and affect the characteristics of cancer, but there are no systematic studies to reveal their prevalent features
    in different cancers.
    Recently, a research team has conducted a systematic study of CAFs and their subtypes in cancer at single-cell resolution, highlighting the potential heterogeneity and plasticity of
    CAFs in cancer biology.

    On November 4, 2022, the team of Luo Han and Xu Heng of West China Hospital of Sichuan University and the Jihwan Park team of Gwangju Institute of Science and Technology in South Korea jointly published a paper entitled "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated" in Nature Communications Fibroblasts in the Tumor Microenvironment"
    The study performed pan-cancer analysis on 226 samples from 10 solid cancers to analyze TME at single-cell resolution, revealing commonality/plasticity of heterogeneous CAFs


    Research background


    Like malignant cells, heterogeneous tumor microenvironment (TME) composites are an important component of
    They interact with malignant cells and form the hallmarks of
    There are different types of nonmalignant cells in TME, mainly fibroblasts, immune cells (such as bone marrow cells, lymphocytes, and macrophages), and endothelial cells
    Previous studies have highlighted the integral role of TME in cancer's biological abilities, such as tumor progression, treatment resistance, angiogenesis induction and metastasis

    Among all types of stromal cells, fibroblasts are the main component of TME, while cancer-associated fibroblasts (CAFs) play a significant tumor-supporting role
    in cancer.
    In addition to interacting directly with malignant epithelial cells, CAFs produce "tumor-permitted" TMEs, including induction of normal fibroblast activation into CAFs, promotion of endothelial cell angiogenesis, recruitment of myeloid cells, and immunosuppressive T cells
    Therefore, CAFs play a key role in shaping TME by interacting with other TME components, showing their potential value
    as prognostic factors and therapeutic targets.
    Recent studies have identified various subtypes of CAFs, but the exact origin of CAFs remains controversial, and their lack of universal characterization hinders targeted therapy
    for CAFs in clinical practice.

    In recent years, the development of single-cell RNA sequencing (scRNA-seq) technology has provided opportunities
    to study cell state fluctuations and cell plasticity strength.
    Characteristics of cancer cells and TME have been analyzed in multiple cancer types, revealing heterogeneity
    of cancer samples of different components at single-cell resolution.
    There have also been recent scRNA-seq-based pan-cancer studies that have analyzed cell numbers under controlled bias, demonstrating the universal characteristics
    of TME cells.
    However, these pan-cancer studies focus only on the properties of immune cells and ignore the interaction
    between different cellular components.

    Overview of the study


    To analyze the TME landscape of solid cancers, the researchers compiled single-cell transcription maps
    of 10 common solid cancer types.
    After strict quality control and filtration, a total of 855,271 cells from 226 samples were included, and a total of 34 TME-related clusters
    were generated by unsupervised clustering.
    Based on typical markers of different cell types, these clusters are divided into 5 major cellular components, including fibroblasts, lymphocytes, myeloid cells, endothelial cells, and plasma cells

    Through CellphoneDB-based analysis, the researchers found that in TME, crosstalk between fibroblasts, endothelial cells, and myeloid cells predominates, while in tumor/adjacent samples, fibroblasts interact most frequently
    with other TME components, regardless of tissue type.
    This suggests that fibroblasts may play an important role
    in cancer biology through communication with other TME components.

    The research team brought together CAFs from all cancer types to explore possible activation processes
    for CAFs.
    Evolutionary trajectories have shown that the main CAFs originate from NFs (normal tissue) and evolve into different states of differentiation that may have different effects on
    The activation trajectories of the main CAF types are divided into three states, exhibit different interactions with other cellular components, and are related to
    the prognosis of immunotherapy.

    In addition, a small portion of CAF components represent alternative sources
    of other TME components, such as endothelial cells and macrophages.
    In particular, the widespread endothelial-mesenchymal transition CAF may interact with macrophages associated with proximal SPP1+ tumors and is associated with
    endothelial-mesenchymal transition and survival stratification.

    Summary of the study


    In conclusion, this study systematically characterizes CAFs in various cancers, not only providing a possible origin for CAFs, but also highlighting the different states
    of CAFs in immunotherapy outcomes and prognosis.
    While further experimental validation is needed to determine the functional role of each CAF cluster and the different origins of CAFs, the researchers say that pan-cancer studies of CAFs may facilitate the development and application
    of future targeted therapies for CAFs.



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