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癌症相关成纤维细胞(CAFs)在实体瘤抗 PD-1/PD-L1 免疫治疗中的作用。

Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers.

机构信息

Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

Henan Institute of Interconnected Intelligent Health Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

出版信息

Mol Cancer. 2023 Feb 10;22(1):29. doi: 10.1186/s12943-023-01731-z.


DOI:10.1186/s12943-023-01731-z
PMID:36759842
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9912573/
Abstract

In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.

摘要

近年来,肿瘤免疫治疗取得了突破性进展。然而,肿瘤免疫治疗,特别是抗 PD-1/PD-L1 免疫检查点抑制剂,在实体瘤中仅对一小部分患者有效。如何提高癌症免疫治疗的效率是一个亟待解决的问题。众所周知,肿瘤微环境(TME)的状态是影响肿瘤免疫治疗效果的重要因素,近年来 TME 中的癌相关成纤维细胞(CAFs)引起了广泛关注。作为 TME 的主要组成部分之一,CAFs 通过分泌细胞因子和囊泡与癌细胞和免疫细胞相互作用,参与 ECM 重塑,最终影响免疫反应过程。随着对 CAFs 异质性的深入研究,为寻找联合免疫治疗的靶点和预测免疫疗效提供了新的策略。在这篇综述中,我们重点关注 CAFs 在实体瘤免疫微环境中的作用,然后进一步阐述 CAFs 影响抗 PD-1/PD-L1 免疫治疗的潜在机制和途径。此外,我们总结了 CAFs 相关靶点和标志物在实体瘤中的潜在临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/37122961606f/12943_2023_1731_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/22c8da8bf067/12943_2023_1731_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/2efb505484d5/12943_2023_1731_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/9fa14af5b1e9/12943_2023_1731_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/37122961606f/12943_2023_1731_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/22c8da8bf067/12943_2023_1731_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/2efb505484d5/12943_2023_1731_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/9fa14af5b1e9/12943_2023_1731_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d82/9912573/37122961606f/12943_2023_1731_Fig4_HTML.jpg

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Naunyn Schmiedebergs Arch Pharmacol. 2025-8-28

[2]
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Biomolecules. 2025-7-27

[3]
Strategies to Overcome PD-1/PD-L1 Blockade Resistance: Focusing on Combination with Immune Checkpoint Blockades.

J Cancer. 2025-7-24

[4]
Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.

Front Immunol. 2025-8-8

[5]
Ordinary differential equation model of cancer-associated fibroblast heterogeneity predicts treatment outcomes.

NPJ Syst Biol Appl. 2025-8-23

[6]
Serum fibrosis marker M2BPGi-based novel score predicts survival of unresectable HCC undergoing immunotherapy.

JHEP Rep. 2025-6-26

[7]
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Nat Rev Clin Oncol. 2025-8-14

[8]
Neurotransmitters: an emerging target for therapeutic resistance to tumor immune checkpoint inhibitors.

Mol Cancer. 2025-8-11

[9]
Combining single-cell and bulk RNA sequencing to identify CAF-related signature for prognostic prediction and treatment response in patients with melanoma.

Sci Rep. 2025-8-8

[10]
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本文引用的文献

[1]
Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.

Nat Commun. 2022-11-4

[2]
Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin.

Cancer Cell. 2022-11-14

[3]
The complex role of tumor-infiltrating macrophages.

Nat Immunol. 2022-8

[4]
Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities.

Nat Rev Drug Discov. 2022-7

[5]
Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer.

Cancer Discov. 2022-6-2

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RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics.

Mol Cancer. 2022-2-21

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Overcoming TGFβ-mediated immune evasion in cancer.

Nat Rev Cancer. 2022-1

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Cancer-associated fibroblasts-derived exosomes promote lung cancer progression by OIP5-AS1/ miR-142-5p/ PD-L1 axis.

Mol Immunol. 2021-12

[9]
Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives.

Mol Cancer. 2021-10-11

[10]
Next frontier in tumor immunotherapy: macrophage-mediated immune evasion.

Biomark Res. 2021-10-9

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