Gu Tao, De Jesus Magdia, Gallagher Heather C, Burris Thomas P, Egilmez Nejat K
Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY, USA.
Department of Biomedical Sciences, University at Albany School of Public Health, Rensselaer, NY, USA.
Oncoimmunology. 2017 Apr 20;6(6):e1319027. doi: 10.1080/2162402X.2017.1319027. eCollection 2017.
An oral sustained-release formulation of Interleukin-10 suppressed tumor growth and enhanced survival in the APC/ spontaneous colon cancer model. Therapeutic benefit was associated with a 5-fold reduction in CD4RORγtFoxp3IL-17 T-helper cell, CD4RORγtFoxp3IL-17 pathogenic T-regulatory cell and CD4RORγtFoxp3IL-17 conventional T-regulatory cell numbers and a concurrent 2-fold enhancement in CD8 T-cell activity in the colon. Selective subset depletion and functional blockade studies demonstrated that at steady-state CD4RORγtIL-17 T-cell subsets and CD4Foxp3 cTreg supported tumorigenesis, whereas CD8 cytotoxic T-lymphocytes impeded tumor progression following IL-10 therapy. Suppression of tumor growth by CD8 T-cells was associated with enhanced tumor infiltration and cytotoxic granule exocytosis. These findings establish the utility of oral IL-10 as a potential new therapeutic in the management of colon cancer and shed light on the cellular mechanisms that underlie its antitumor activity.
白细胞介素-10的口服缓释制剂在APC/自发性结肠癌模型中可抑制肿瘤生长并提高生存率。治疗益处与结肠中CD4RORγtFoxp3IL-17辅助性T细胞、CD4RORγtFoxp3IL-17致病性调节性T细胞和CD4RORγtFoxp3IL-17常规调节性T细胞数量减少5倍以及CD8 T细胞活性同时增强2倍相关。选择性亚群耗竭和功能阻断研究表明，在稳态下，CD4RORγtIL-17 T细胞亚群和CD4Foxp3 cTreg支持肿瘤发生，而CD8细胞毒性T淋巴细胞在IL-10治疗后阻碍肿瘤进展。CD8 T细胞对肿瘤生长的抑制与肿瘤浸润增强和细胞毒性颗粒胞吐有关。这些发现确立了口服IL-10作为结肠癌治疗潜在新疗法的效用，并揭示了其抗肿瘤活性背后的细胞机制。
