Cytokines in cancer immunity and immunotherapy

Smyth, Mark J.; Cretney, Erika; Kershaw, Michael H.; Hayakawa, Yoshihiro

doi:10.1111/j.0105-2896.2004.00199.x

Cited by 360 publications

(274 citation statements)

References 183 publications

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“…Inflammatory mediators, such as COX-2 and cytokines, enhance tumorigenesis through the activation of multiple signaling pathways in tumor tissue (17,37). IL6 is a major proinflammatory cytokine that participates in inflammation-associated carcinogenesis (38,39) and has been reported to be positively linked with angiogenesis, EMT, and poor prognosis in esophageal cancer (20).…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence has indicated that inflammatory responses are important for cancer development (15,16). An increase in inflammatory mediators, such as COX-2 and proinflammatory cytokines has been shown to lead to tumor promotion, invasion, angiogenesis, and inflammation-associated intestinal tumorigenesis (17)(18)(19). In our previous study, IL6 has been demonstrated to link with aggressive tumor behavior and poor prognosis of esophageal SCC (20).…”

Section: Introductionmentioning

confidence: 94%

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1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The aim of this study was to highlight the role of 1a,25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL6 levels, and tumor progression by a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition, and inhibited IL6 signaling. In the 4-NQOinduced esophageal tumor animal model, increased IL6 and MDSC recruitment were linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL6, the induction of MDSCs, and the incidence of 4-NQO-induced invasive tumors. Moreover, the IL6-induced changes in C57 mice, including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T-cell proliferation, which were abrogated by calcitriol supplementation. On the basis of our results, we concluded that calcitriol abrogated the IL6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D 3 may be a promising strategy for the prevention and treatment of esophageal SCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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“…17 A range of tumor antigens has also been targeted using vaccines or adoptively transferred T cells. 18 However, with the exception of melanoma, tumors have proved to be poorly immunogenic thus far.…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity of dual-specific T cells and influenza virus

et al. 2007

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“…Among a continuous growing list of cytokines with antitumor potential (1), interleukin (IL)-15 appears as a candidate with especially promising features (2,3).…”

Section: Introductionmentioning

confidence: 99%

An Antibody Fusion Protein for Cancer Immunotherapy Mimicking IL-15 trans-Presentation at the Tumor Site

Kermer

Baum²,

Hornig³

et al. 2012

Molecular Cancer Therapeutics

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Cytokines driving the immune response are powerful tools for cancer immunotherapy, but their application is generally limited by severe systemic toxicity. Targeted approaches by means of antibodycytokine fusion proteins might enable focus on the cytokine activity to the tumor site, thereby reducing unwanted side effects. Here, we investigated the possibility to improve the efficiency of interleukin (IL)-15 presentation in a targeted approach by the incorporation of an IL-15Ra chain fragment, mimicking physiologic trans-presentation. Therefore, an antibody cytokine fusion protein (scFv_RD_IL-15) composed of an antibody moiety targeting the tumor stromal fibroblast activation protein (FAP), an extended IL15Rasushi domain (RD) and IL-15 was generated, exhibiting antibody-mediated specific binding and cytokine activity in soluble and targeted form. Comparative analysis with a corresponding antibody fusion protein devoid of RD (scFv_IL-15) showed for scFv_RD_IL-15 in solution enhanced stimulatory activity on Mo7e (IL-15Rbg) cells and reduced proliferation response on CTLL-2 (IL-15Rabg) cells, while in FAPtargeted, that is, membrane-bound form, comparable proliferation of CTLL-2 (IL-15Rabg) cells was obtained. In addition, scFv_RD_IL-15 achieved in its soluble and target-bound form stronger proliferation and cytotoxicity on unstimulated and activated T cells, respectively. Furthermore, in vivo analysis in a lung metastasis tumor mouse model revealed a superior antitumor effect for scFv_RD_IL-15 in comparison with that obtained by an untargeted or RD missing version of IL-15 fusion protein. Thus, tumor-directed transpresentation of IL-15 in association with RD in form of an antibody fusion protein seems to be a promising approach to further improve the antitumor effect of IL-15.

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Cytokines in cancer immunity and immunotherapy

Cited by 360 publications

References 183 publications

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Antitumor activity of dual-specific T cells and influenza virus

An Antibody Fusion Protein for Cancer Immunotherapy Mimicking IL-15 trans-Presentation at the Tumor Site

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