Cancer associated fibroblasts: An essential role in the tumor microenvironment

Tao, Leilei; Huang, Guichun; Song, Haiyan; Chen, Yitian; Chen, Longbang

doi:10.3892/ol.2017.6497

Cited by 279 publications

(219 citation statements)

References 120 publications

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“…The tumor microenvironment is shown to be composed of extracellular matrix and stromal cells, such as cancer‐associated fibroblasts (CAFs), the main cell types constituting the tumor stroma . Emerging evidence has shown that CAFs are critical for remodeling the tumor microenvironment and ultimately affect tumor initiation and progression . Aberrant secretion of cytokines to tumor site is one of the features of CAFs.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 Emerging evidence has shown that CAFs are critical for remodeling the tumor microenvironment and ultimately affect tumor initiation and progression. 7,8 Aberrant secretion of cytokines to tumor site is one of the features of CAFs. It is acknowledged that cytokines serve as mediators in shaping tumor microenvironment and facilitating tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

137

113

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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

137

113

View full text Add to dashboard Cite

show abstract

“…1A) [58]. While the mechanism of immunosuppression is not fully understood in PDAC, we do know that activated pancreatic stellate cells and fibroblasts impair immuno-surveillance, contributing to local immune suppression [59]. Moreover, an effective immune activation in the PDAC microenvironment has to overcome the presence of Foxp3 + Tregs (immunologically “cold”), secretion of anti-inflammatory cytokines, expression of checkpoint inhibitors [58].…”

Section: Future Discovery To Develop Nanotherapy For Pdac and Other Smentioning

confidence: 99%

Use of nano engineered approaches to overcome the stromal barrier in pancreatic cancer

Meng

Nel

2018

Advanced Drug Delivery Reviews

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While chemotherapy is the only approved non-surgical option for the majority of pancreatic cancer patients, it rarely results in a cure. The failure to respond to chemotherapy is due to the presence of an abundant dysplastic stroma that interferes in drug delivery and as a result of drug resistance. It is appropriate, therefore, to consider the stromal contribution to the resistance to chemotherapy and sidestepping this barrier with nanocarriers that improve survival outcome. In this paper, we provide a short overview of the role of the stroma in chemotherapy resistance, including the use of nanocarriers to negate this barrier. We provide a perspective and guidance towards the implementation of nanotherapeutic approaches to improve therapeutic delivery and efficacy of PDAC management.

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“…In return, CAF populations emanate paracrine signals that affect cancer progression. Bi‐directional cross‐talk between cancer cells and fibroblasts is presumed to be the leading cause of malignant cancer phenotype formation …”

Section: From the Solid Base Of A Paradigm To A Flimsy But Falsifiablmentioning

confidence: 99%

Missed Druggable Cancer Hallmark: Cancer–Stroma Symbiotic Crosstalk as Paradigm and Hypothesis for Cancer Therapy

Sverdlov

2018

BioEssays

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During tumor evolution, cancer cells use the tumor-stroma crosstalk to reorganize the microenvironment for maximum robustness of the tumor. The success of immune checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer treatment should not aim to influence the individual components of super complex intracellular interactomes (molecular targeting), but try to disrupt the intercellular interactions between cancer and stromal cells, thus breaking the tumor as a whole. Arguments are provided in favor of a hypothesis that such interactions include formation of synapse-like structures (interfaces) where the interacting cells are located at a distance of ∼10-15 nm. Within these interfaces, molecules initiating and strengthening the interaction are organized, and allow optimum cross-signaling; a very confined intercellular space facilitates the concentration of secreted cytokines, enhancing the paracrine cross-communication. These features of tumors form a druggable cancer hallmark the tumor-stroma symbiotic crosstalk-which represents a new target for efficient cancer drug discovery.

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Cancer associated fibroblasts: An essential role in the tumor microenvironment

Cited by 279 publications

References 120 publications

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Use of nano engineered approaches to overcome the stromal barrier in pancreatic cancer

Missed Druggable Cancer Hallmark: Cancer–Stroma Symbiotic Crosstalk as Paradigm and Hypothesis for Cancer Therapy

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