Th9 cells are a subset of CD4+ Th cells that produce the pleiotropic cytokine IL-9. IL-9/Th9 can function as both positive and negative regulators of immune response, but the role of IL-9/Th9 in tumor immunity is unknown. We examined the role of IL-9/Th9 in a model of pulmonary melanoma in mice. Lack of IL-9 enhanced tumor growth, while tumor-specific Th9 cell treatment promoted stronger antitumor responses in both prophylactic and therapeutic models. Th9 cells also elicited strong host antitumor CD8+ CTL responses by promoting Ccl20/Ccr6-dependent recruitment of DCs to the tumor tissues. Subsequent tumor antigen delivery to the draining LN resulted in CD8+ T cell priming. In agreement with this model, Ccr6 deficiency abrogated the Th9 cell–mediated antitumor response. Our data suggest a distinct role for tumor-specific Th9 cells in provoking CD8+ CTL-mediated antitumor immunity and indicate that Th9 cell–based cancer immunotherapy may be a promising therapeutic approach.
Yong Lu, Sungyoul Hong, Haiyan Li, Jungsun Park, Bangxing Hong, Lijuan Wang, Yuhuan Zheng, Zhiqiang Liu, Jingda Xu, Jin He, Jing Yang, Jianfei Qian, Qing Yi
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Pulmonary interstitial macrophages are required to mediate the pro-tumorigenic effects of IL-9
Yongyao Fu, Jocelyn Wang, Baohua Zhou, Hongyu Gao, Huaxin Zhou, Amanda Fisher, David Omstead, Sabrina Khan, Lei Han, Abigail Pajulas, Jean-Christophe Renauld, Sophie Paczesny, Yunlong Liu, Lei Yang, Robert Tighe, Paula Licona-Limón, Richard Flavell, Shogo Takatsuka, Daisuke Kitamura, Jie Sun, Basar Bilgicer, Catherine Sears, Kai Yang, Mark Kaplan |
Nature Communications | 2022 |
Epigenetic Regulation: A Link between Inflammation and Carcinogenesis
B Vezzani, M Carinci, M Previati, S Giacovazzi, M Sala, R Gafà, G Lanza, M Wieckowski, P Pinton, C Giorgi |
Cancers | 2022 |
Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy
M Khelil, Y Godet, S Abdeljaoued, C Borg, O Adotévi, R Loyon |
Cancers | 2022 |
The Roles of IRF-8 in Regulating IL-9-Mediated Immunologic Mechanisms in the Development of DLBCL: A State-of-the-Art Literature Review
M Cai, N Chen |
Frontiers in Oncology | 2022 |
Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients
E West, K Scott, E Tidswell, K Bendjama, N Stojkowitz, M Lusky, M Kurzawa, R Prasad, G Toogood, C Ralph, D Anthoney, A Melcher, F Collinson, A Samson |
Cancers | 2022 |
Potentiating adoptive cell therapy using synthetic IL-9 receptors
A Kalbasi, M Siurala, L Su, M Tariveranmoshabad, L Picton, P Ravikumar, P Li, J Lin, H Escuin-Ordinas, T Da, S Kremer, A Sun, S Castelli, S Agarwal, J Scholler, D Song, P Rommel, E Radaelli, R Young, W Leonard, A Ribas, C June, K Garcia |
Nature | 2022 |
IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer
Heim L, Yang Z, Tausche P, Hohenberger K, Chiriac MT, Koelle J, Geppert CI, Kachler K, Miksch S, Graser A, Friedrich J, Kharwadkar R, Rieker RJ, Trufa DI, Sirbu H, Neurath MF, Kaplan MH, Finotto S |
Frontiers in immunology | 2022 |
First Characterization of Chicken Interleukin-9
He S, Chen L, Hao X, Yang Y, Shang S |
Frontiers in immunology | 2022 |
IRF8: Mechanism of Action and Health Implications.
Moorman HR, Reategui Y, Poschel DB, Liu K |
Cells | 2022 |
Opposing functions of circadian protein DBP and atypical E2F family E2F8 in anti-tumor Th9 cell differentiation
Park SA, Lim YJ, Ku WL, Zhang D, Cui K, Tang LY, Chia C, Zanvit P, Chen Z, Jin W, Wang D, Xu J, Liu O, Wang F, Cain A, Guo N, Nakatsukasa H, Wu C, Zhang YE, Zhao K, Chen W |
Nature Communications | 2022 |
Neglected, yet significant role of FOXP1 in T-cell quiescence, differentiation and exhaustion
Kaminskiy Y, Kuznetsova V, Kudriaeva A, Zmievskaya E, Bulatov E |
Frontiers in immunology | 2022 |
IL-1β promotes IL-9-producing Th cell differentiation in IL-2-limiting conditions through the inhibition of BCL6
Canaria DA, Clare MG, Yan B, Campbell CB, Ismaio ZA, Anderson NL, Park S, Dent AL, Kazemian M, Olson MR |
Frontiers in immunology | 2022 |
Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors
Chen T, Xue Y, Wang S, Lu J, Zhou H, Zhang W, Zhou Z, Li B, Li Y, Wang Z, Li C, Eloy Y, Sun H, Shen Y, Diarra MD, Ge C, Chai X, Mou H, Lin P, Yu X, Ye Z |
Bioactive Materials | 2022 |
PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells.
Gerlach K, Popp V, Wirtz S, Al-Saifi R, Gonzalez Acera M, Atreya R, Dregelies T, Vieth M, Fichtner-Feigl S, McKenzie ANJ, Rosenbauer F, Weigmann B, Neurath MF |
Journal of Crohn's & colitis | 2022 |
Distinct T helper cell-mediated antitumor immunity: T helper 2 cells in focus
Silva RC, Lopes MF, Travassos LH |
2022 |