A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells

Xia, Siyuan; Wei, Jun; Wang, Jingya; Sun, Huayan; Zheng, Wenting; Li, Yangguang; Sun, Yanbo; Zhao, Hang; Zhang, Song; Wen, Ti; Zhou, Xinglong; Gao, Jianxin; Wang, Puyue; Wu, Zhenzhou; Zhao, Lingyun; Yin, Zhinan

doi:10.1189/jlb.0713371

Cited by 29 publications

(26 citation statements)

References 44 publications

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“…39 This may, however, be explained by the addition of IFNg in incubation protocols of that study, which is known to induce CCL22 in epithelial cells. 41,42 Although the regulation of CCL22 has been investigated in several further studies, 3,6,35,43 we describe here for the first time its induction through IL-1a by cancer cells. Further, we show that IL-1a-induced CCL22 leads to the recruitment of Treg and this can be blocked by the IL-1 receptor antagonist anakinra.…”

Section: Discussionmentioning

confidence: 99%

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

et al. 2016

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In cancer patients, immunosuppression through regulatory T cells (Treg) is a crucial component of tumor immune evasion and contributes to disease progression. Tumor-infiltrating Treg in particular suppress local effector T cell responses and are associated with poor prognosis in tumors such as human pancreatic cancer or hepatocellular carcinoma (HCC). The chemokine CCL22 is known to recruit Treg into the tumor tissue and many types of human tumors are known to express high levels of CCL22. The mechanisms leading to intratumoral secretion of CCL22 are so far unknown. We demonstrate here that intratumoral CCL22 is induced in tumor-infiltrating immune cells through cancer cell-derived interleukin-1 (IL-1a). In pancreatic cancer and HCC, CCL22 is produced by intratumoral dendritic cells, while the cancer cells themselves do not secrete CCL22 in vitro and in vivo. Incubation of human peripheral blood mononuclear cells (PBMC) or murine splenocytes with tumor cells or tumor cell supernatants strongly induced CCL22 secretion in vitro. Tumor cell supernatants contained IL-1 and CCL22 induction in PBMC could be specifically prevented by the IL-1 receptor antagonist anakinra or by transfection of tumor cell lines with IL-1 siRNA, leading to a suppression of Treg migration. In conclusion, we identify here tumor cell-derived IL-1a as a major inducer of the Treg attracting chemokine CCL22 in human cancer cells. Therapeutic blockade of the IL-1 pathway could represent a promising strategy to inhibit tumorinduced immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

et al. 2016

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“…Based on the antiinflammatory activity of IL-37, several studies have been performed to investigate whether the administration of IL-37 may ameliorate chronic inflammation [57]. Studies performed in patients reported an overall increase of circulating as well as tissue IL-37 in inflammatory bowel disease [58], systemic lupus erythematosus [59], Graves' disease [60] and AS [61]. With regard to experimental arthritis, systemic and intra-articular administration of recombinant IL-37 was able to inhibit the development of synovitis by reducing pro-inflammatory cytokines and modulating Th17 cells [62,63].…”

Section: Il-37mentioning

confidence: 99%

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

et al. 2017

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In recent years, the landscape of pro- and anti-inflammatory cytokines has rapidly expanded with the identification of new members proven to be involved at different extent in the pathogenesis of chronic immune mediated inflammatory diseases including rheumatoid arthritis (RA). The advance of our understanding of mediators involved in the pathogenesis of RA and in consequence, the development of novel targeted therapies is necessary to provide patients not responding to currently available strategies with novel compounds. The aim of this review article is to provide an overview on recently identified cytokines, emphasizing their pathogenic role and therapeutic potential in RA. A systematic literature review was performed to retrieve articles related to every cytokine discussed in the review. In some cases, evidence from animal models and RA patients is already consistent to move forward into drug development. In others, conflicting observation and the paucity of data require further investigations.Forty years after the discovery of IL-1, the landscape of cytokines is continuously expanding with increasing possibilities to develop novel therapeutic strategies in RA. Electronic supplementary material The online version of this article (10.1186/s41927-017-0001-8) contains supplementary material, which is available to authorized users.

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“…A recent study using IL-27R −/− mice revealed that the number of Treg cells was reduced in TME [12]; while another study using mice with IL-27 conditionally deleted in DC revealed that DC-derived IL-27 recruited Treg into TME [54]. In another study [55], DC-derived IL-27 is shown to induce a Treg population that express CD39 and CD69, which inhibits T-cell responses via generation of adenosine.…”

Section: Role Of Il-27 In Modulating Treg Responses and Its Implicationmentioning

confidence: 99%

The Yin and Yang Aspects of IL-27 in Induction of Cancer-Specific T-Cell Responses and Immunotherapy

Liu

et al. 2015

Immunotherapy

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Accumulating evidences from animal studies have indicated that both endogenous and exogenous IL-27, an IL-12 family of cytokine, can increase antitumor T-cell activities and inhibit tumor growth. IL-27 can modulate Treg responses, and program effector T cells into a unique T-effector stem cell (TSEC) phenotype, which enhances T-cell survival in the tumor microenvironment. However, animal studies also suggest that IL-27 induces molecular pathways such as IL-10, PD-L1 and CD39, which may downregulate tumor-specific T-cell responses. In this review paper, we will discuss the Yin and Yang aspects of IL-27 in the induction of tumor-specific T-cell responses, and the potential impacts of these functions of IL-27 in the design of cancer immunotherapy.

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A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells

Cited by 29 publications

References 44 publications

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

The Yin and Yang Aspects of IL-27 in Induction of Cancer-Specific T-Cell Responses and Immunotherapy

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