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癌症相关成纤维细胞:异质性、致瘤性及治疗靶点。

Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets.

作者信息

Lv Keke, He Tianlin

机构信息

Department of Hepatopanreatobiliary Surgery, Changhai Hospital, 168 Changhai Road, Yangpu District, Shanghai, 200433, China.

出版信息

Mol Biomed. 2024 Dec 16;5(1):70. doi: 10.1186/s43556-024-00233-8.


DOI:10.1186/s43556-024-00233-8
PMID:39680287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11649616/
Abstract

Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven to be a formidable challenge, yielding limited success on a broad scale. The tumor microenvironment(TME), a critical niche for cancer cell survival, presents a novel way for cancer treatment. Cancer-associated fibroblast (CAF), as a main component of TME, is a dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span the entire spectrum of tumor development, metastasis, drug resistance, and prognosis. A thorough understanding of CAFs functions and therapeutic advances holds significant clinical implications. In this review, we underscore the heterogeneity of CAFs by elaborating on their origins, types and function. Most importantly, by elucidating the direct or indirect crosstalk between CAFs and immune cells, the extracellular matrix, and cancer cells, we emphasize the tumorigenicity of CAFs in cancer. Finally, we highlight the challenges encountered in the exploration of CAFs and list targeted therapies for CAF, which have implications for clinical treatment.

摘要

癌症以免疫逃逸、活跃代谢和高度增殖为特征,由基质和细胞组成。尽管研究一直聚焦于实质细胞,但非实质成分也不容忽视。事实证明,靶向癌症实质细胞是一项艰巨的挑战,在广泛范围内取得的成功有限。肿瘤微环境(TME)是癌细胞生存的关键生态位,为癌症治疗提供了一种新途径。癌症相关成纤维细胞(CAF)作为TME的主要成分,是一种动态演变、具有双重功能的基质细胞。此外,它们的生物活性贯穿肿瘤发展、转移、耐药性和预后的全过程。全面了解CAF的功能和治疗进展具有重要的临床意义。在这篇综述中,我们通过阐述CAF的起源、类型和功能来强调其异质性。最重要的是,通过阐明CAF与免疫细胞、细胞外基质和癌细胞之间的直接或间接相互作用,我们强调了CAF在癌症中的致瘤性。最后,我们突出了在探索CAF过程中遇到的挑战,并列出了针对CAF的靶向治疗方法,这对临床治疗具有启示意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/d9fcf8c15d59/43556_2024_233_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/2e6724642d6c/43556_2024_233_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/3e0a5df47bc5/43556_2024_233_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/69a68cf3116c/43556_2024_233_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/d9fcf8c15d59/43556_2024_233_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/2e6724642d6c/43556_2024_233_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/3e0a5df47bc5/43556_2024_233_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/69a68cf3116c/43556_2024_233_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a56/11649616/d9fcf8c15d59/43556_2024_233_Fig4_HTML.jpg

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[2]
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[3]
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[4]
Integrated multiomics analysis identifies PHLDA1+ fibroblasts as prognostic biomarkers and mediators of biological functions in pancreatic cancer.

Front Immunol. 2025-7-4

[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development.

Nat Commun. 2024-6-11

[2]
Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response.

Cell Rep. 2024-5-28

[3]
Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer.

Nat Commun. 2024-4-27

[4]
Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma therapy: Challenges and opportunities.

Cancer Lett. 2024-6-1

[5]
The nanobody targeting PD-L1 and CXCR4 counteracts pancreatic stellate cell-mediated tumour progression by disrupting tumour microenvironment.

Int Immunopharmacol. 2024-5-10

[6]
Single dual-specific anti-PD-L1/TGF-β antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.

Int J Surg. 2024-5-1

[7]
Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer.

Clin Transl Med. 2024-3

[8]
TGFβ-specific T cells induced by a TGFβ-derived immune modulatory vaccine both directly and indirectly modulate the phenotype of tumor-associated macrophages and fibroblasts.

J Immunother Cancer. 2024-2-27

[9]
Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.

Clin Cancer Res. 2024-5-1

[10]
Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Nano Lett. 2024-3-20

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