Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity

Li, Tuanjie; Yi, Shuhong; Liu, Wei; Jia, Changchang; Wang, Guoying; Hua, Xuefeng; Tai, Yan; Zhang, Qi; Chen, Guihua

doi:10.1007/s12032-013-0663-z

Cited by 92 publications

(68 citation statements)

References 31 publications

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“…This effect was dependent on both cell‐to‐cell contact and prostaglandin E2 (PGE2) released by TAFs. Another group confirmed our results by analyzing TAFs from HCC and colorectal carcinomas . Our study also suggested that NK cells present in melanoma lesions may reside in proximity to fibroblasts surrounding tumor nests, further suggesting a role for TAF in the inhibition of NK‐cell function in vivo .…”

Section: Tumor Microenvironment and The Evasion From Nk‐cell Attacksupporting

confidence: 86%

Effect of tumor cells and tumor microenvironment on NK‐cell function

et al. 2014

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The ability of tumors to manage an immune-mediated attack has been recently included in the "next generation" of cancer hallmarks. In solid tumors, the microenvironment that is generated during the first steps of tumor development has a pivotal role in immune regulation. An intricate net of cross-interactions occurring between tumor components, stromal cells, and resident or recruited immune cells skews the possible acute inflamma-tory response toward an aberrant ineffective chronic inflammatory status that favors the evasion from the host's defenses. Natural killer (NK) cells have powerful cytotoxic activity , but their activity may be eluded by the tumor microenvironment. Immunosubversion, immunoediting or immunoselection of poorly immunogenic tumor cells and interference with tumor infiltration play a major role in evading NK-cell responses to tumors. Tumor cells, tumor-associated fibroblasts and tumor-induced aberrant immune cells (i.e. tolero-genic or suppressive macrophages, dendritic cells (DCs) and T cells) can interfere with NK-cell activation pathways or the complex receptor array that regulate NK-cell activation and antitumor activity. Thus, the definition of tumor microenvironment-related immuno-suppressive factors, along with the identification of new classes of tissue-residing NK-like innate lymphoid cells, represent key issues to design effective NK-cell-based therapies of solid tumors.

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Section: Tumor Microenvironment and The Evasion From Nk‐cell Attacksupporting

confidence: 86%

Effect of tumor cells and tumor microenvironment on NK‐cell function

et al. 2014

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“…Finally, it is important to point out that a pioneer study involving CAFs isolated from melanoma, but also other studies involving hepatocellular and colorectal carcinoma-derived fibroblasts, have shown that these cells can decrease NKp30, NKp44, DNAM-1 and/or NKG2D expression at the surface of NK cells, as well as PFN or GzmB expression [34–36]. These effects seem to be dependent, at least partially, on the secretion of PGE2 and IDO by CAFs and lead to an attenuate cytotoxic activity of NK cells against their tumor target cells.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the secretion of several chemokines by CAFs (including CXCL12/SDF1 and CCL2/MCP-1) can potentially attract macrophages in the tumor microenvironment and induce their differentiation into an M2 immunosuppressive phenotype [30, 31], and also allow the recruitment of immunosuppressive MDSC populations in the stroma [32, 33]. Finally, studies involving melanoma, hepatocellular and colorectal carcinoma-derived fibroblasts have shown that CAFs can decrease the expression of several NK activating receptors (including NKp30, NKp44 and NKG2D) on the NK cell surface through the secretion of prostaglandin E2 (PGE2) and/or indoleamine-2,3-dioxygenase (IDO) [34–36] leading to an attenuate cytotoxic activity of NK cells against their tumor target cells.…”

Section: Introductionmentioning

confidence: 99%

Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion

et al. 2017

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Cancer-associated fibroblasts (CAFs) play a central role in the complex process of tumor-stroma interaction and promote tumor growth. Emerging evidences also suggest that these fibroblasts are involved in the alteration of the anti-tumor immune response by impacting several immune cell populations, especially through their secretion of pro-inflammatory and immunosuppressive factors in the tumor microenvironment. However, the underlying immuno-modulating mechanisms triggered by these fibroblasts are still only partially defined. In this study, we provide evidence that melanoma-associated fibroblasts decrease the susceptibility of melanoma tumor cells to NK-mediated lysis through the secretion of active matrix metalloproteinases. This secretion reduces the expression of the two NKG2D ligands, MICA/B, at the surface of tumor cells and consequently decreases the NKG2D-dependent cytotoxic activity of NK cells against melanoma tumor cells. Together, our data demonstrate that the modification of tumor cell susceptibility to killer cells is an important determinant of the anti-tumor immune response alteration triggered by CAFs.

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“…67 In addition, CAFs significantly suppressed the cytotoxicity function of NK cells via releasing PGE2 in melanoma. 68 In the presence of NK cells, the CAF-induced expression of PGE2 was higher than fibroblasts, 64 suggesting that NK cells can also influence the cytokine expression of CAFs. However, studies of the influence of NK cells on CAFs are limited, and further studies are needed.…”

Section: Interaction Between Cancer-associated Fibroblasts and Mastmentioning

confidence: 99%

Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

Liu

Chen

et al. 2019

J Cellular Molecular Medi

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Multiple studies have shown that cancer‐associated fibroblasts (CAFs) play an important role in tumour progression, including carcinogenesis, invasion, metastasis and the chemoresistance of cancer cells. Immune cells, including macrophages, natural killer cells, dendritic cells and T cells, play a dual role in the tumour microenvironment. Although increasing research has focused on studying interactions between distinct cells in the tumour microenvironment, the complex relationships between CAFs and immune cells remain unclear and need further study. Here, we summarize our current understanding of crosstalk between CAFs and immune cells, which may help clarify their diagnostic and therapeutic value in tumour progression.

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Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity

Cited by 92 publications

References 31 publications

Effect of tumor cells and tumor microenvironment on NK‐cell function

Effect of tumor cells and tumor microenvironment on NK‐cell function

Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion

Crosstalk between cancer‐associated fibroblasts and immune cells in cancer

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