Cancer-associated fibroblasts: Just on the opposite side of antitumour immunity?

Guo, Shuaiqingying; Yuan, Jing; Meng, Xiaolin; Feng, Xue; Ma, Ding; Han, Yingyan; Li, Kezhen

doi:10.1016/j.intimp.2023.110601

Cited by 5 publications

(3 citation statements)

References 90 publications

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“…Thus, SCLC with high CAF infiltration seemly presents an “immune hot” profile. Actually, although the immunosuppressive function of CAFs has been prevalently reported, some studies also revealed their immune activation function 40 , 41 . Additionally, as widely recognized, CAFs were great heterogenous with context-dependent function 16 .…”

Section: Discussionmentioning

confidence: 99%

Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer

Lu,

Li,

Zhao

et al. 2024

Sci Rep

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Small cell lung cancer (SCLC) is heterogenous in phenotype and microenvironment. Dynamic phenotypic reprogramming, leading to heterogeneity, is prevalent in SCLC, while the mechanisms remain incompletely understood. Cancer-associated fibroblasts (CAFs) possess comprehensive roles in cancer progression, while their function in phenotypic reprogramming of SCLC remain elusive. Here, we obtained transcriptome data of SCLC tissues from publicly available databases, subsequently estimated abundance of CAFs. We found CAF-abundant SCLC exhibited non-neuroendocrine (Non-NE) characteristics. Supporting this, the positive correlation of expression level of α-SMA, the CAF marker, and expression level of REST, protein typically expressed in Non-NE type SCLC, was identified in SCLC tissue arrays. Moreover, we revealed that fibroblasts inhibited NE markers expression and cell proliferation of SCLC cells in the co-culture system comprising lung fibroblasts and SCLC cells, indicating a phenotypic reprogramming from NE to Non-NE. During this process, fibroblast-derived IL-6 activated the JAK2/STAT3 signaling, upregulated c-MYC expression, and subsequently activated the NOTCH pathway, driving phenotypic reprogramming. Moreover, CAF-enriched SCLC exhibited increased immune cell infiltration, elevated expression of immune activation-related signatures, and checkpoint molecules. Our data also highlighted the chemoresistance induced by fibroblasts in SCLC cells, which was effectively reversed by JAK inhibitor. In conclusion, fibroblasts induced phenotypic reprogramming of SCLC cells from NE to Non-NE, likely contributes to inflamed immune microenvironment and chemoresistance. These findings provide novel insights into the clinical implications of CAFs in SCLC.

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Section: Discussionmentioning

confidence: 99%

Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer

Lu,

Li,

Zhao

et al. 2024

Sci Rep

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“…According to the mutation analysis, CAFs are genetically more stable than tumor cells, making them a better target for therapy. CAF genes, which are responsible for the secretion of TGF-β, MMPs, hepatocyte growth factor (HGF), and tenascin-C (Tn-C), were identified as promising therapeutic targets ( Guo S. et al, 2023 ; Greimelmaier et al, 2023 ; Li and Mu, 2023 ; Yang et al, 2023 ). The combined treatment protocol with radiotherapy and TGF-β inhibitors chemotherapy was found to be effective for attenuation of tumor cell proliferation and spreading ( Bouquet et al, 2011 ).…”

Section: Effects Of Radiation Therapy On Cancer-associated Fibroblast...mentioning

confidence: 99%

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Zhao,

Mo,

Neganova

et al. 2023

Front. Cell Dev. Biol.

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Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors.

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“…A considerable amount of research has indicated that CAFs play an essential role in regulating tumor initiation, growth, metastasis, and drug resistance ( Eckert et al, 2019 ; Zhang et al, 2023a ; Huang et al, 2023 ). For example, CAFs secrete a multitude of cytokines and metabolic products, engaging in crosstalk with tumor cells and other stromal cells, thereby suppressing immune cell function and promoting tumor progression ( Guo et al, 2023 ). In recent years, it has also been revealed that CAFs play a role in antigen cross-presentation.…”

Section: Introductionmentioning

confidence: 99%

Mapping knowledge structure and themes trends of cancer-associated fibroblasts: a text-mining study

Cheng,

Li,

et al. 2023

Front. Mol. Biosci.

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Introduction: Cancer-associated fibroblasts (CAFs) constitute an important component of the tumor microenvironment, participating in various facets of cancer advancement and being recognized as contributors to tumor immune evasion. The role of CAFs in various tumor types has attracted increasing attention recently. In this work, we conducted a comprehensive bibliometric analysis to uncover research trajectories and highlight emerging areas in the field of CAFs.Methods: A systematic search was performed within the Web of Science Core Collection to identify articles/reviews on CAFs published between 2000 and 2023. Leveraging advanced bibliometric tools such as VOSviewer, CiteSpace, and online website, we examined and visualized publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and noteworthy references, keywords, and genes.Results: Our analysis included 5,190 publications, indicating a rapid growth trend in both annual publications and citations related to CAFs. China and the United States emerged as the foremost contributors in terms of publications, funding agencies, and international collaborations. Breast cancer was the most studied tumor, followed by colorectal cancer, pancreatic cancer, prostate cancer, and gastric cancer. Based on co-occurrence and bursting keywords, we identified the following research topics including immune cells (T cells, B-cells, tumor-associated macrophages), tumor immune microenvironment (antitumor immunity, immune infiltration, immunosuppression), immunotherapy (PD-L1), microRNAs (miRNA), extracellular vesicles (exosome), multiple tumors (pancreatic ductal adenocarcinoma, bladder cancer, head and neck squamous cell carcinoma), antitumor agents (gemcitabine, cisplatin resistance), bioinformatics (pan-cancer), epithelial-mesenchymal transition (stemness), FAPI PET/CT, DNA methylation, etc., may receive sustained attention in the future. Furthermore, TGFB1, IL-6, TNF, TP53, and VEGFA emerged as the top 5 genes that have garnered the greatest research attention in the field of CAFs. The KEGG enrichment analysis highlighted that the top 20 most studied genes were mainly associated with HIF-1 and Toll-like receptor signaling pathways.Discussion: In sum, our bibliometric analysis offers a comprehensive overview of the research landscape in the field of CAFs. It encompasses the current state, evolving patterns, and prospective avenues of exploration, with special attention to the potential advancements in tumor immune microenvironment.

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Cancer-associated fibroblasts: Just on the opposite side of antitumour immunity?

Cited by 5 publications

References 90 publications

Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer

Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Mapping knowledge structure and themes trends of cancer-associated fibroblasts: a text-mining study

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