Experimental Lung Metastases in Mice Are More Effectively Inhibited by Blockade of IL23R than IL23
| Autor: | Juming Yan, Xian-Yang Li, Dipti Vijayan, Stacey Allen, Daniel J. Cua, Kazuyoshi Takeda, Mark J. Smyth, Jing Liu, Heidi Harjunpää, Michele W.L. Teng |
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| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Cancer Research Lung Neoplasms medicine.medical_treatment Immunology Interleukin-23 Interferon-gamma 03 medical and health sciences 0302 clinical medicine Blocking antibody Tumor Cells Cultured medicine Animals Receptor Mice Knockout biology Chemistry Receptors Interleukin Xenograft Model Antitumor Assays Immune checkpoint Killer Cells Natural Mice Inbred C57BL Interleukin 10 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Interleukin 12 Cancer research biology.protein Immunotherapy Antibody CD8 |
| Zdroj: | Cancer Immunology Research. 6:978-987 |
| ISSN: | 2326-6074 2326-6066 |
| DOI: | 10.1158/2326-6066.cir-18-0011 |
| Popis: | Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10. IL23 is a cytokine that negatively affects antitumor immunity. In this study, we investigated whether IL23-deficient (IL23p19−/−) and IL23R-deficient (IL23R−/−) mice phenocopied each other, with respect to their tumor control. We found that IL23R−/− mice had significantly fewer lung metastases compared with IL23p19−/− mice across three different experimental lung metastasis models (B16F10, LWT1, and RM-1). Similarly, IL23R blocking antibodies were more effective than antibodies neutralizing IL23 in suppressing experimental lung metastases. The antimetastatic activity of anti-IL23R was dependent on NK cells and IFNγ but independent of CD8+ T cells, CD4+ T cells, activating Fc receptors, and IL12. Furthermore, our data suggest this increased antitumor efficacy was due to an increase in the proportion of IFNγ-producing NK cells in the lungs of B16F10 tumor-bearing mice. Anti-IL23R, but not anti-IL23p19, partially suppressed lung metastases in tumor-bearing mice neutralized for IL12p40. Collectively, our data imply that IL23R has tumor-promoting effects that are partially independent of IL23p19. Blocking IL23R may be more effective than neutralizing IL23 in the suppression of tumor metastases. Cancer Immunol Res; 6(8); 978–87. ©2018 AACR. |
| Databáze: | OpenAIRE |
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