Interleukin-4 and CpG oligonucleotide therapy suppresses the outgrowth of tumors by activating tumor-specific Th1-type immune responses

Kajiwara, Atsushi; Doi, Hiroyoshi; Eguchi, Junichi; Ishii, Shigeaki; Hiraide-Sasagawa, Ayako; Sakaki, Masashi; Omori, Risa; Hiroishi, Kazumasa; Imawari, Michio

doi:10.3892/or.2012.1723

Cited by 7 publications

(3 citation statements)

References 22 publications

(26 reference statements)

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“…In this regard, cytotoxic T lymphocytes (CTLs) play a central role in the immunosurveillance and clearance of both intracellular pathogens and malignant cells (20,21). On the other hand, Th1 cells play a critical role in the immune system's challenge with tumors (22). Some studies also indicated the importance of dendritic cells (DCs) as APC for presenting tumor antigens to CTLs or CD4 + T cells (23).…”

Section: Discussionmentioning

confidence: 99%

Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model

Yazdi¹,

Mahdavi²,

Faghfuri³

et al. 2015

Iran J Biotech

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Section: Discussionmentioning

confidence: 99%

Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model

Yazdi¹,

Mahdavi²,

Faghfuri³

et al. 2015

Iran J Biotech

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“…IL4 also plays a pivotal role in antibody isotype switching and stimulates the production of IgE. This cytokine has been applied in the treatment of autoimmune disorder like multiple myeloma [3], cancer [4], psoriasis [5], and arthritis [6]. IL4 has also been extensively applied to inhibit detrimental effect of Th1 [7].…”

Section: Introductionmentioning

confidence: 99%

Prediction of IL4 Inducing Peptides

Dhanda

Gupta

Vir

et al. 2013

Clinical and Developmental Immunology

239

149

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The secretion of Interleukin-4 (IL4) is the characteristic of T-helper 2 responses. IL4 is a cytokine produced by CD4+ T cells in response to helminthes and other extracellular parasites. It has a critical role in guiding antibody class switching, hematopoiesis and inflammation, and the development of appropriate effector T-cell responses. In this study, it is the first time an attempt has been made to understand whether it is possible to predict IL4 inducing peptides. The data set used in this study comprises 904 experimentally validated IL4 inducing and 742 noninducing MHC class II binders. Our analysis revealed that certain types of residues are preferred at certain positions in IL4 inducing peptides. It was also observed that IL4 inducing and noninducing epitopes differ in compositional and motif pattern. Based on our analysis we developed classification models where the hybrid method of amino acid pairs and motif information performed the best with maximum accuracy of 75.76% and MCC of 0.51. These results indicate that it is possible to predict IL4 inducing peptides with reasonable precession. These models would be useful in designing the peptides that may induce desired Th2 response.

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“…These data suggest an intriguing duality of IL4 function; host-derived IL4 seems to contribute to tumor control, while tumor-derived IL4 contributes to tumor growth. Other groups have investigated the role of tumor-derived IL4 in shaping the TME and impacting tumor growth, however, these models involved expression of IL4 under control of viral promoters that results in supraphysiological levels of IL4 (37, 38). In contrast, we provide the first reported insight into the relative contribution of host- versus tumor-derived IL4 using a model system that expresses endogenous levels of IL4.…”

Section: Discussionmentioning

confidence: 99%

IL4 Limits the Efficacy of Tumor-Targeted Antibody Therapy in a Murine Model

Surana

Wang

et al. 2014

Cancer Immunology Research

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Tumor-targeted antibody therapy has had a major impact on reducing morbidity and mortality in a wide range of cancers. Antibodies mediate their antitumor activity in part by activating immune effector cells; however, the tumor microenvironment (TME) is enriched with cellular and soluble mediators that actively suppress generation of antitumor immunity. Here, we investigate the potential of prospectively identifying and neutralizing an immunomodulatory soluble mediator within the TME to enhance therapeutic efficacy of the HER2-directed antibody trastuzumab. Using the D5-HER2 cell line and an immunocompetent human HER2 transgenic animal (hmHER2Tg) in which human HER2 is a self-antigen, we determined that IL4 was present in the TME and produced by both tumor and stromal cells. A siRNA-based screening approach identified Stat5a as a novel negative regulator of IL4 production by D5-HER2 tumor cells. Furthermore, IL4 neutralization using the anti-IL4 antibody 11B11 enhanced the efficacy of trastuzumab and modulated the TME. For example, IL4 neutralization resulted in reduced levels of myeloid chemoattractants CCL2, CCL11, and CXCL5 in the TME. Combination therapy with 11B11 and trastuzumab resulted in a reduction of tumor-infiltrating CD11b+CD206+ myeloid cells compared to monotherapy. These data suggest that IL4 neutralization enhances the efficacy of trastuzumab by influencing the phenotype of myeloid cells within the TME and provides further rationale for combining tumor-targeted antibody therapy with agents that neutralize factors in the TME that suppress generation of productive antitumor immune responses.

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Interleukin-4 and CpG oligonucleotide therapy suppresses the outgrowth of tumors by activating tumor-specific Th1-type immune responses

Cited by 7 publications

References 22 publications

Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model

Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model

Prediction of IL4 Inducing Peptides

IL4 Limits the Efficacy of Tumor-Targeted Antibody Therapy in a Murine Model

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