The Role of Interleukin-9 in Cancer

Lee, Jacob E; Zhu, Ziwen; Bai, Qian; Brady, Tucker J; Xiao, Hualiang; Wakefield, Mark R.; Fang, Yujiang

doi:10.1007/s12253-019-00665-6

Cited by 16 publications

(11 citation statements)

References 45 publications

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“…The function of IL9 in tumor immunity is controversial [52][53][54]. It has been generally suggested that IL9 may inhibit the growth of solid tumors by activating the innate or adaptive immune response [55,56], while as a lymphocyte growth factor it may promote progression of hematological malignancies [10,12].…”

Section: Discussionmentioning

confidence: 99%

“…It has been generally suggested that IL9 may inhibit the growth of solid tumors by activating the innate or adaptive immune response [55,56], while as a lymphocyte growth factor it may promote progression of hematological malignancies [10,12]. However, since IL9 has also been reported to promote proliferation of multiple solid tumor models (like pancreatic cancer, lung cancer and colitis associated cancer) [57][58][59], its anti-cancer activity may be context and tumor type specific [52][53][54].…”

Section: Discussionmentioning

confidence: 99%

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Antibody-based delivery of Interleukin-9 to neovascular structures: therapeutic evaluation in cancer and arthritis

Gouyou

Ongaro

Cazzamalli

et al. 2020

Preprint

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Interleukin-9 (IL9) is a cytokine with multiple functions, including the ability to activate group 2 innate lymphoid cells (ILC2s), which has been postulated to be therapeutically active in mouse models of arthritis. Similarly, IL9 has been suggested to play an important role in tumor immunity. Here, we describe the cloning, expression and characterization of three fusion proteins based on murine IL9 and the F8 antibody, specific to the alternatively-spliced EDA domain of fibronectin. EDA is strongly expressed in cancer and in various arthritic conditions, while being undetectable in the majority of healthy organs. IL9-based fusion proteins with an irrelevant antibody specific to hen egg lysozyme served as negative control in our study. The fusion proteins were characterized by quantitative biodistribution analysis in tumor-bearing mice using radioiodinated protein preparations. The highest tumor uptake and best tumor:organ ratios were observed for a format, in which the IL9 moiety was flanked by two units of the F8 antibody in single-chain Fv format. Biological activity of IL9 was retained when the payload was fused to antibodies. However, the targeted delivery of IL9 to the disease site resulted in a modest anti-tumor activity in three different murine models of cancer (K1735M2, CT26 and F9), while no therapeutic benefit was observed in a collagen induced model of arthritis. Collectively, these results confirm the possibility to deliver IL9 to the site of disease but cast doubts about the alleged therapeutic activity of this cytokine in cancer and arthritis, which has been postulated in previous publications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antibody-based delivery of Interleukin-9 to neovascular structures: therapeutic evaluation in cancer and arthritis

Gouyou

Ongaro

Cazzamalli

et al. 2020

Preprint

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“…Interleukin-9 (IL-9) is a pleiotropic cytokine whose gene is located on the long arm of chromosome 5 [11]. Specific secretion of IL-9 is observed not only in T helper type 2 (Th2) cells but also in activated Th9 cells, Th17 cells, regulatory T cells, and mast cells [12].…”

Section: Introductionmentioning

confidence: 99%

“…When IL-9 binds to its receptor, activation of JAK1 and JAK3 kinases is induced, and as a result, signal transducer and activator of transcription 1 (STAT-1), STAT-3, STAT-5 pathways are triggered [19]. Gene expression of IL-9 is controlled by phosphorylated STAT molecules in the nucleus, where they bind to regulatory sequences and provide pleiotropic biological functions of IL-9 [11,20].…”

Section: Introductionmentioning

confidence: 99%

“…It has been clarified that IL-9 plays an important role in different inflammation processes and autoimmune diseases [21]. Interestingly, recent research has suggested that IL-9 can have both a protumorigenic and antitumorigenic role in the pathogenesis of neoplasia [11,[21][22][23]. This dichotomous function of IL-9 has been described in various cancer diseases.…”

Section: Introductionmentioning

confidence: 99%

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The Role of IL-9 Polymorphisms and Serum IL-9 Levels in Carcinogenesis and Survival Rate for Laryngeal Squamous Cell Carcinoma

Pašvenskaitė

Liutkevičienė

Gedvilaitė

et al. 2021

Cells

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Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients’ five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients’ survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.

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