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Author: Mia
Introduction: Cancer-related fibroblasts (CAFs) are the main components of the tumor microenvironment (TME) and affect the characteristics of cancer, but no systematic research has been conducted to reveal their common characteristics in different cancers. Recently, a research team conducted a systematic study of CAFs and their subtypes in cancer at single-cell resolution, emphasizing the potential heterogeneity and plasticity of CAFs in cancer biology.
On November 4, 2022, West China Hospital of Sichuan University Luo Han and Xu Heng's team and Jihwan Park team from Gwangju School of Science and Technology, South Korea jointly published a research paper titled "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fiberbroblasts in the tumor microenvironment" on Nature Communications. The study conducted pan-cancer analysis on 226 samples of 10 solid carcinomas, analyzing TME at single-cell resolution, revealing the commonality/plasticity of heterogeneous CAFs.
https://doi.org/10.1038/s41467-022-34395-2
Research background
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Like malignant cells, heterogeneous tumor microenvironment (TME) composites are also an important part of tumors. They interact with malignant cells to form the characteristics of cancer. There are different types of non-malignant cells in TME, mainly including fibroblasts, immune cells (such as bone marrow cells, lymphocyte and macrophage ) and endothelial cells . Previous studies have highlighted the indispensable role of TME in cancer's biological capabilities, such as tumor progression, therapeutic resistance, angiogenesis induction and metastasis.
In all types of stromal cells, fibroblasts are the main component of TME, while cancer-associated fibroblasts (CAFs) play a significant tumor support role in cancer. In addition to directly interacting with malignant epithelial cells, CAFs can also produce "tumor-permitted" TMEs, including inducing normal fibroblast activation to CAFs, promoting endothelial angiogenesis, recruiting myeloid cells, and immunosuppressing T cell . Therefore, CAFs play a key role in shaping TMEs 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 is still controversial, and its lack of universal characterization hinders the targeted treatment of CAFs in clinical practice .
In recent years, the development of single-cell RNA sequencing (scRNA-seq) technology has provided opportunities for studying cell state fluctuations and cell plasticity intensity. Characteristics of cancer cells and TMEs have been analyzed in multiple types of cancer, revealing the heterogeneity of cancer samples in different components at single-cell resolution. There are also recent pan-cancer studies based on scRNA-seq, which analyses the number of cells under controllable bias, demonstrating the general characteristics of TME cells. However, these pan-cancer studies of only focus on the characteristics of immune cells and ignore the interaction between different cellular components .
Research Overview
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To analyze the TME landscape of solid cancer, 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. Depending on the 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 crosstalk between fibroblasts, endothelial cells and myeloid cells dominate in TMEs, while in tumor/neighboring samples, fibroblasts interact with other TME components most frequently regardless of tissue type. This suggests that fibroblasts may play an important role in cancer biology through communication with other TME components .
research team brought together all cancer types of CAFs to explore possible activation processes for CAFs.Evolutionary trajectory shows that the main CAFs of originated from NFs (normal tissue) and evolved into different differentiation states, which may have different effects on TME. The activation trajectory of the main CAF type of is divided into three states, showing different interactions with other cellular components and is related to the prognosis of immunotherapy for .
In addition, a small percentage 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 be associated with macrophage interactions associated with proximal SPP1+ tumors, and is associated with endothelial-mesenchymal transition and survival stratification.
study summary diagram
study summary
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In summary, this study systematically describes the characteristics of CAFs in various cancers, not only providing the possible origin of 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 research on CAFs may promote the development and application of targeted CAFs in the future.
Reference materials:
https://doi.org/10.1038/s41467-022-34395-2
Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital for treatment.
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