Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

An, Yuan-Yuan; Liu, Fengtian; Chen, Ying; Yang, Qing

doi:10.1111/jcmm.14745

Cited by 79 publications

(72 citation statements)

References 120 publications

(276 reference statements)

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“…In our study, we also isolated two subtypes of CAFs, apCAFs and the traditional myCAFs. Previous studies suggested that apCAFs could activate CD4+ T cells and act as the immune-modulator [50]. We found the ratio of apCAF/myCAF in primary tumor tissue was dramatically higher than that in pulmonary metastatic and recurrent tumor tissues, suggestive of the difference of the TME of OS in the primary versus the metastatic tumor.…”

Section: Discussionmentioning

confidence: 59%

Single-cell RNA-seq reveals identity and heterogeneity of malignant osteoblast cells and TME in osteosarcoma

Zhou

2020

Preprint

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25Osteosarcoma (OS) has high heterogeneity and poor prognosis. In order to explore the 26 molecular mechanism of OS and the tumor micro-environment (TME) on OS, we 27 employed single-cell RNA-sequencing (scRNA-seq) on 110,745 individual cells from 28 65 chromosomal lesions, including structural variations (SVs) and copy number 66 alterations (CNAs); however, few recurrent point mutations in protein-encoding genes 67 have been identified in OS [11][12][13][14][15].Low expression of immune-associated genes is 68 another significant phenotype for OS [16]. How to convert the immunosuppressive 69 microenvironment into the one that favors the induction of antitumor immunity is 70 indispensable for effective cancer immunotherapy. 71Here, we employed single cell transcriptome approach to dissect the 72 heterogeneity of OS cells. We analyzed the transcriptomic profiles of a total of 73 110745 cells from 7 primary tumors, 2 lung metastatic and 2 recurrent OS tissues. We 74 first divided the OS cells into 5 sub-clusters and osteoclast into 3 subtypes. The 75 profiles of OS, OC and immune-system cells were analyzed. We found that the TME 76 of the recurrent and lung metastatic OS exhibited more significant suppressivity than 77 primary tumor tissue. Thus, the results in this study improve the understanding of the 78 immune-suppressivity observed in advanced OS including distant metastasis and 79 recurrence, and are potentially valuable in novel treatment strategy for OS. 80Of importance, we are the first to uncover that Treg cells in OS expressed 81 TIGIT. TIGIT is a coinhibitory receptor expressed on effector T cells, natural killer 82 (NK) cells, T regulatory cells (Treg) and T follicular helper (TFH) cells. It has gained 83 attention as a potential therapeutic target in wide variety of tumors[17-19]. The 84 antibodies of TIGIT, named BGB-A1217, had registered and recruited on August 85 2019. Here we explored the preclinical significance of blocking of TIGIT. 86 Method 87 Patients 88 The eleven patients for scRNA-seq analysis enrolled in this study were hospitalized 89 during the period of The study was approved by Shanghai Sixth People's Hospital Ethics Committee. Each 91 patient was provided a written signed consent. All patients were diagnosed according 92 to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines 93 in Oncology with the terms of Bone Cancer (Version 2.2019). Among 11 patients for 94 scRNA-seq, 7 were derived from the primary sites of patients who received traditional 95 first line combination chemotherapy for OS, including Adriamycin(ADM), 96 cisplatin(DDP), methotrexate(MTX) and Ifosfamide(IFO) and surgical therapy. 2 lung 97 metastatic patients and 2 recurrent patients all received the gemcitabine combined 98 with Docetaxel(GT) chemotherapy treatment. The BC17, one of the lung metastasis 99 patients, had enrolled in clinical trial NCT03676985 and undergone the anti-PD-L1 100 treatment for 6 times. For this clinical trial, all enrolled patients had finished the 101 neoadjuvant...

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Section: Discussionmentioning

confidence: 59%

Single-cell RNA-seq reveals identity and heterogeneity of malignant osteoblast cells and TME in osteosarcoma

Zhou

2020

Preprint

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“…For example, activated CAFs account for up to 90% of total PDAC tumor volume [ 6 , 9 , 41 ]. Activated CAFs are known to support tumor growth and secrete chemokines and cytokines like TGFβ, vascular endothelial growth factor-A (VEGF-A), other angiogenic factors, prostaglandin-2 (PGE2), and indolamine-2,3-dioxygenase (IDO) to promote immunosuppression, where the latter is known to be secreted by inflammatory CAFs [ 6 , 9 , 40 , 42 , 43 ]. Increased TGFβ and VEGF-A secretion by CAFs also increases regulatory T-cell (T-reg) infiltration in adenocarcinomas [ 43 ].…”

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

“…Activated CAFs are known to support tumor growth and secrete chemokines and cytokines like TGFβ, vascular endothelial growth factor-A (VEGF-A), other angiogenic factors, prostaglandin-2 (PGE2), and indolamine-2,3-dioxygenase (IDO) to promote immunosuppression, where the latter is known to be secreted by inflammatory CAFs [ 6 , 9 , 40 , 42 , 43 ]. Increased TGFβ and VEGF-A secretion by CAFs also increases regulatory T-cell (T-reg) infiltration in adenocarcinomas [ 43 ]. TGFβ, PGE2, and IDO are also known to downregulate NCRs and inhibit cytokine secretion from NK cells [ 44 ], thus decreasing their cytotoxicity.…”

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma

Malchiodi

Weiner

2021

Cancers

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Interactions between natural killer (NK) cells and cancer-associated fibroblasts (CAFs) comprise a relevant but relatively understudied crosstalk relationship within the tumor microenvironment (TME). This review discusses the relevance of both natural killer cell and cancer-associated fibroblast function and activity in cancers, with an emphasis on pancreatic ductal adenocarcinoma (PDAC), incorporating additional insights from other malignancies to inform future directions for research. We describe what is currently known about NK cell-CAF crosstalk and their molecular interactions, how it is possible to exploit NK cell cytotoxicity in tumors and how to target CAFs to enhance efficacy of cancer therapies and cytotoxic immune cells. Although not previously tested in combination, there is an abundance of evidence demonstrating that targeting tumor-promoting CAFs and exploiting NK cells, separately, are beneficial as therapeutic strategies. This raises the possibility that a novel combination regimen addressing these two cell targets may be even more beneficial to eradicate PDAC and other solid tumors.

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“…Growing evidence has shown that the TME is one of the key determinants of the tumor immune response, and CAFs are closely associated with the efficacy of immunotherapy [161]. CAFs directly interact with immune cells by secreting growth factors, cytokines and chemokines, thus mediating and regulating the infiltration of immune cells [162]. In addition, CAFs can also create a physical immune barrier through ECM remodeling to exert immunomodulatory effects [163].…”

Section: Mirnas In Cafs and Cancer Immunosuppressionmentioning

confidence: 99%

The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives

Fang

Zhang

et al. 2020

J Hematol Oncol

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As the most important component of the stromal cell population in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are crucial players in tumor initiation and progression. The interaction between CAFs and tumor cells, as well as the resulting effect, is much greater than initially expected. Numerous studies have shown that noncoding RNAs (ncRNAs) play an irreplaceable role in this interplay, and related evidence continues to emerge and advance. Under the action of ncRNAs, normal fibroblasts are directly or indirectly activated into CAFs, and their metabolic characteristics are changed; thus, CAFs can more effectively promote tumor progression. Moreover, via ncRNAs, activated CAFs can affect the gene expression and secretory characteristics of cells, alter the TME and enhance malignant biological processes in tumor cells to contribute to tumor promotion. Previously, ncRNA dysregulation was considered the main mechanism by which ncRNAs participate in the crosstalk between CAFs and tumor cells. Recently, however, exosomes containing ncRNAs have been identified as another vital mode of interaction between these two types of cells, with a more direct and clear function. Gaining an in-depth understanding of ncRNAs in CAFs and the complex regulatory network connecting CAFs with tumor cells might help us to establish more effective and safer approaches for cancer therapies targeting ncRNAs and CAFs and offer new hope for cancer patients.

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Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

Cited by 79 publications

References 120 publications

Single-cell RNA-seq reveals identity and heterogeneity of malignant osteoblast cells and TME in osteosarcoma

Single-cell RNA-seq reveals identity and heterogeneity of malignant osteoblast cells and TME in osteosarcoma

Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma

The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives

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