Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer

Graziano, F; Ruzzo, Annamaria; Canestrari, Emanuele; Loupakis, Fotios; Santini, Daniele; Rulli, Eliana; Humar, Bostjan; Galluccio, Nadia; Bisonni, Renato; Floriani, Irene; Maltese, Paolo Enrico; Falcone, Alfredo; Tonini, Giuseppe; Catalano, Vincenzo; Fontana, Andrea; Giustini, Lucio; Masi, Gianluca; Vincenzi, Bruno; Alessandroni, Paolo; Magnani, Mauro

doi:10.1038/tpj.2008.16

Cited by 25 publications

(20 citation statements)

References 32 publications

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“…IL-1a, a key inflammatory cytokine, has been reported to be produced by various cancer cells derived from pancreas, lung, ovary and stomach, and to increase the invasive and metastatic capabilities of tumor cells [23,24]. Our data indicate that IL-1a secreted by SCC cells may enhance the CTSK expression of the surrounding Fbs in a paracrine fashion, which turns out to augment the invasive ability of SCC cells with support from CTSK-bearing Fbs.…”

Section: Discussionmentioning

confidence: 55%

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Xie¹,

Moroi²,

Hayashida³

et al. 2011

Journal of Dermatological Science

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Section: Discussionmentioning

confidence: 55%

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Xie¹,

Moroi²,

Hayashida³

et al. 2011

Journal of Dermatological Science

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“…20,21 Among these, single nucleotide polymorphisms (SNPs) from IL-3, IL-6R, IL-8 and, interestingly, IL-15 were found to be associated with an increased colon cancer risk, 22 while IL-1 or IL-1 receptor antagonist polymorphisms negatively impact on CRC survival and recurrence. 23,24 The role of the inflammatory milieu is of particular importance in CRC as the risk of developing dysplasia and CRC positively correlates with the duration and degree of inflammation in patients with irritable bowel disease (IBD). 25 While there is abundant evidence indicating the causal relationship of chronic mucosal inflammation with CRC, 26 the mechanism(s) underlying this correlation, namely the role of IL-15-mediated signaling, remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

IL-15 suppresses colitis-associated colon carcinogenesis by inducing antitumor immunity

et al. 2015

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IL-15 regulates the development, survival, and proliferation of multiple innate and adaptive immune cells and plays a dual role, inducing both tumor cell growth and antitumor immunity. However, the role of IL-15 in inflammation-induced cancer remains unclear. To explore this, we have compared the colon carcinoma burden of Il15 ¡/¡ and Il15ra ¡/¡ mice with wild type (WT) mice after induction of colitis-associated colon carcinogenesis utilizing the AOM/DSS model. Compared to WT mice, Il15¡/¡ but not Il15ra ¡/¡ mice showed reduced survival, along with higher tumor incidence, colon weight, and tumor size. This suggests that low affinity IL-15 signaling via the shared IL-2Rb/gc decreases the risk for developing colitis-associated cancer. CD11c-Il15 mice, in which IL-15 expression is reconstituted in Il15 ¡/¡ mice under the control of the CD11c-promoter, showed that selective reconstitution of IL-15 in antigen-presenting cells restored the CD8 C T and NK cell compartments, serum levels of IFNg, G-CSF, IL-10, and CXCL1 and reduced tumor burden. After demonstrating IL-15 expression in human colorectal cancer (CRC) cells in situ, we investigated the role of this cytokine in the modulation of key colonic oncogenic pathways in the tumor. While these pathways were found to be unaltered in the absence of IL-15, tumor transcriptome analysis showed that the loss of IL-15 upregulates key inflammatory mediators associated with colon cancer progression, such as IL-1b, IL-22, IL-23, Cxcl5, and Spp1. These findings provide evidence that IL-15 suppresses colitis-associated colon carcinogenesis through regulation of antitumor cytotoxicity, and modulation of the inflammatory tumor micromilieu.

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“…Also, it may play important roles in tumor progression and prediction of patient survival in patients with cervical squamous cell carcinoma (48,49). Previously, high IL-1RA levels have been associated, in certain studies, with greater disease severity (49,50), while in other studies with lesser disease severity (51,52).…”

Section: Cancer Investigationmentioning

confidence: 99%

Salivary Immunosuppressive Cytokines IL-10 and IL-13 Are Significantly Elevated in Oral Squamous Cell Carcinoma Patients

Aziz¹,

Ahmed²,

Ali³

et al. 2015

Cancer Investigation

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Oral squamous cell carcinoma (OSCC) is considered to be one of the most fatal diseases worldwide, owing to its late diagnosis and lack of availability of established reliable biomarkers. The aim of this study was to highlight the significance of immunosuppressive cytokines as potential biomarkers in OSCC. Whole unstimulated saliva was collected from each individual (30 OSCC patients and 33 age- and gender-matched healthy controls). Immunosuppressive cytokines, including IL-4, IL-10, IL-13, and IL-1RA, were evaluated in each sample using Luminex multianalyte profiling (xMAP) technology on BioPlex instrument. Our results showed that all the studied salivary cytokines were raised in OSCC patients as compared to controls, where IL-10 and IL-13 salivary levels showed statistically significant difference (p = .004 and p = .010, respectively). Mean levels of salivary cytokines in three histologically defined OSCC categories, compared employing one-way ANOVA, showed that salivary levels of IL-1RA were highest in patients having poorly differentiated OSCC tumors as compared to those having moderately and well-differentiated tumors (p = .000 and p = .002, respectively). Among OSCC individuals, duration of smokeless tobacco correlated positively with IL-1RA (p = .036). We conclude that salivary levels of immunosuppressive cytokines, IL-4, IL-10, IL-13, and IL-1RA, could prove to be potential biomarkers of OSCC and can be further investigated as markers of early detection and disease progression.

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Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer

Cited by 25 publications

References 32 publications

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α

IL-15 suppresses colitis-associated colon carcinogenesis by inducing antitumor immunity

Salivary Immunosuppressive Cytokines IL-10 and IL-13 Are Significantly Elevated in Oral Squamous Cell Carcinoma Patients

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