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- Publisher Website: 10.1186/s13046-019-1326-5
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- PMID: 31409352
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Article: Soluble fibrinogen-like protein 2 promotes the growth of hepatocellular carcinoma via attenuating dendritic cell-mediated cytotoxic T cell activity
Title | Soluble fibrinogen-like protein 2 promotes the growth of hepatocellular carcinoma via attenuating dendritic cell-mediated cytotoxic T cell activity |
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Authors | |
Keywords | Soluble fibrinogen-like protein 2 Hepatocellular carcinoma Tumor microenvironment Dendritic |
Issue Date | 2019 |
Publisher | BioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home |
Citation | Journal of Experimental and Clinical Cancer Research, 2019, v. 38, p. article no. 351 How to Cite? |
Abstract | Background:
Soluble fibrinogen-like protein 2 (sFGL2), a secretory protein expressed by regulatory T cells (Tregs) with immunosuppressive activity, is highly expressed in both the peripheral blood and tumor tissue of patients with hepatocellular carcinoma (HCC); however, sFGL2 function in HCC remains largely unknown. Here, we elucidated the potential role of sFGL2 in HCC progression.
Methods:
T cells, dendritic cells (DCs), and related cytokines in the tumor microenvironment were comparatively analyzed in BALB/c and C57BL/6 mice bearing transplanted hepatomas harboring Fgl2-knockout or receiving sFGL2-antibody treatment. Additionally, the effects of sFGL2 on DCs and T cells were evaluated in vivo and ex vivo.
Results:
The growth of both subcutaneously and orthotopically transplanted hepatomas was inhibited in Fgl2-knockout mice and those treated with the sFGL2 antibody, respectively, as compared with controls. Moreover, sFGL2 depletion enhanced the proportion and cytotoxicity of cytotoxic T cells, promoted DC maturation, and improved DC activity to proliferate T cells in the tumor microenvironment. Furthermore, we detected lower levels of interleukin (IL)-35 in both types of transplanted hepatomas and higher level of IL-6 in orthotopically transplanted hepatomas following sFGL2 depletion. Mechanistically, we found that sFGL2 impaired bone-marrow-derived DC (BMDCs) function by inhibiting phosphorylation of Akt, nuclear factor-kappaB, cAMP response element binding protein, and p38 and downregulating the expression of major histocompatibility complex II, CD40, CD80, CD86, and CD83 on BMDCs in vitro.
Conclusions:
Our data suggest that sFGL2 promotes hepatoma growth by attenuating DC activity and subsequent CD8+ T cell cytotoxicity, suggesting sFGL2 as a novel potential therapeutic target for HCC treatment. |
Persistent Identifier | http://hdl.handle.net/10722/275107 |
ISSN | 2023 Impact Factor: 11.4 2023 SCImago Journal Rankings: 2.806 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yang, M | - |
dc.contributor.author | Zhang, Z | - |
dc.contributor.author | Chen, J | - |
dc.contributor.author | Xu, M | - |
dc.contributor.author | Huang, J | - |
dc.contributor.author | Wang, M | - |
dc.contributor.author | Li, W | - |
dc.contributor.author | Wan, X | - |
dc.contributor.author | Yuen, MF | - |
dc.contributor.author | Luo, X | - |
dc.contributor.author | Xi, D | - |
dc.contributor.author | Ning, Q | - |
dc.date.accessioned | 2019-09-10T02:35:36Z | - |
dc.date.available | 2019-09-10T02:35:36Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Journal of Experimental and Clinical Cancer Research, 2019, v. 38, p. article no. 351 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.uri | http://hdl.handle.net/10722/275107 | - |
dc.description.abstract | Background: Soluble fibrinogen-like protein 2 (sFGL2), a secretory protein expressed by regulatory T cells (Tregs) with immunosuppressive activity, is highly expressed in both the peripheral blood and tumor tissue of patients with hepatocellular carcinoma (HCC); however, sFGL2 function in HCC remains largely unknown. Here, we elucidated the potential role of sFGL2 in HCC progression. Methods: T cells, dendritic cells (DCs), and related cytokines in the tumor microenvironment were comparatively analyzed in BALB/c and C57BL/6 mice bearing transplanted hepatomas harboring Fgl2-knockout or receiving sFGL2-antibody treatment. Additionally, the effects of sFGL2 on DCs and T cells were evaluated in vivo and ex vivo. Results: The growth of both subcutaneously and orthotopically transplanted hepatomas was inhibited in Fgl2-knockout mice and those treated with the sFGL2 antibody, respectively, as compared with controls. Moreover, sFGL2 depletion enhanced the proportion and cytotoxicity of cytotoxic T cells, promoted DC maturation, and improved DC activity to proliferate T cells in the tumor microenvironment. Furthermore, we detected lower levels of interleukin (IL)-35 in both types of transplanted hepatomas and higher level of IL-6 in orthotopically transplanted hepatomas following sFGL2 depletion. Mechanistically, we found that sFGL2 impaired bone-marrow-derived DC (BMDCs) function by inhibiting phosphorylation of Akt, nuclear factor-kappaB, cAMP response element binding protein, and p38 and downregulating the expression of major histocompatibility complex II, CD40, CD80, CD86, and CD83 on BMDCs in vitro. Conclusions: Our data suggest that sFGL2 promotes hepatoma growth by attenuating DC activity and subsequent CD8+ T cell cytotoxicity, suggesting sFGL2 as a novel potential therapeutic target for HCC treatment. | - |
dc.language | eng | - |
dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home | - |
dc.relation.ispartof | Journal of Experimental and Clinical Cancer Research | - |
dc.rights | Journal of Experimental and Clinical Cancer Research. Copyright © BioMed Central Ltd. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Soluble fibrinogen-like protein 2 | - |
dc.subject | Hepatocellular carcinoma | - |
dc.subject | Tumor microenvironment | - |
dc.subject | Dendritic | - |
dc.title | Soluble fibrinogen-like protein 2 promotes the growth of hepatocellular carcinoma via attenuating dendritic cell-mediated cytotoxic T cell activity | - |
dc.type | Article | - |
dc.identifier.email | Yuen, MF: mfyuen@hku.hk | - |
dc.identifier.authority | Yuen, MF=rp00479 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1186/s13046-019-1326-5 | - |
dc.identifier.pmid | 31409352 | - |
dc.identifier.pmcid | PMC6693134 | - |
dc.identifier.scopus | eid_2-s2.0-85070747151 | - |
dc.identifier.hkuros | 304368 | - |
dc.identifier.volume | 38 | - |
dc.identifier.spage | article no. 351 | - |
dc.identifier.epage | article no. 351 | - |
dc.identifier.isi | WOS:000480773000002 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1756-9966 | - |