Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity

Morimoto, Masahiro; Kishida, Tsunao; Nakano, Hiroshi; Yoshimoto, Koichiro; Shin‐Ya, Masaharu; Shimada, Taketoshi; Nakai, Shigeru; Imanishi, Jirô; Yoshimoto, Takayuki; Hisa, Yasuo; Mazda, Osam

doi:10.1158/0008-5472.can-08-2793

Cited by 87 publications

(77 citation statements)

References 51 publications

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“…Hypopharyngeal carcinoma has one of the worst prognoses among HNSCCs, and the 5-year survival rate is approximately 30% to 35% (3). Hypopharyngeal carcinoma is prominently invasive, and total pharyngolaryngectomy, which is the curative surgical treatment, causes serious functional problems that include vocal, swallowing, and chewing disorders (4). In addition, hypopharyngeal carcinoma often metastasizes to lymph nodes or distant organs, and therefore innovations to improve disease survival and larynx preservation are needed.…”

Section: Introductionmentioning

confidence: 99%

RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

Arai

Chano²,

Futami³

et al. 2011

Cancer Research

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RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyperrecombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers. Cancer Res; 71(13); 4598-607. Ó2011 AACR.

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Section: Introductionmentioning

confidence: 99%

RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

Arai

Chano²,

Futami³

et al. 2011

Cancer Research

Self Cite

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“…Exogenous IL-27 is shown to exert potent antitumor activity against transplanted murine tumors through multiple mechanisms, including activating CTL or NK cells, or its antiangiogenic activity (25)(26)(27). However, the contribution of endogenous IL-27 to tumor progression has not been studied.…”

mentioning

confidence: 99%

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

Wei

Xia

Sun

et al. 2013

The Journal of Immunology

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Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene–induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell–dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.

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“…No significant difference in IL-35 expression was identified between relapsed and nonrelapsed patients. (17,19). However, distinct from other members of the IL-12 family, IL-35 is a novel inhibitory cytokine and suppresses T cell proliferation through the unconventional signal transducer and activator of transcription (STAT) 1-STAT4 heterodimer signaling pathway (18).…”

Section: The Association Between Il-35 Expression and The Prognosis Omentioning

confidence: 99%

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

Jiang

et al. 2017

Oncology Letters

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Abstract. has been proposed as a novel immune-suppressing cytokine. However, the function of IL-35 in malignant diseases is yet to be elucidated. The present study investigated IL-35 expression levels in laryngeal squamous cell carcinoma (LSCC) tissues and the peripheral blood of patients to explore the potential involvement of IL-35 in LSCC progression. In the present study, IL-35 expression levels in tissues and peripheral blood were analyzed by reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The association between IL-35 expression levels and clinical characteristics was also evaluated. The present results demonstrated that IL-35 expression in tumor tissues was significantly higher than in adjacent normal tissues, and a significant association between IL-35 expression levels in tissues and the tumor site was detected. Furthermore, the expression of IL-35 in the peripheral blood of patients was significantly decreased subsequent to tumor resection. No correlation between peripheral blood IL-35 expression and clinical characteristics was detected. In conclusion, the present study demonstrated that IL-35 is highly expressed in LSCC tissues and in the peripheral blood of patients with LSCC. There was a notable, significant reduction of peripheral blood IL-35 expression following surgical resection of tumors. These results may be useful for diagnostic or therapeutic purposes in patients with LSCC.

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Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity

Cited by 87 publications

References 51 publications

RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

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