| First Author | Jiang Y | Year | 2019 |
| Journal | J Immunother Cancer | Volume | 7 |
| Issue | 1 | Pages | 28 |
| PubMed ID | 30717817 | Mgi Jnum | J:307122 |
| Mgi Id | MGI:6459082 | Doi | 10.1186/s40425-018-0494-8 |
| Citation | Jiang Y, et al. (2019) TNF-alpha enhances Th9 cell differentiation and antitumor immunity via TNFR2-dependent pathways. J Immunother Cancer 7(1):28 |
| abstractText | Tumor specific Th9 cells are potential effector cells for adoptive therapy of human cancers. TNF family members OX40L, TL1A and GITRL have been shown to promote the induction of Th9 cells and antitumor immunity. However, the role of TNF-alpha, the prototype of the TNF superfamily cytokines, in Th9 cell differentiation and their antitumor efficacy is not defined. Here, we showed that TNF-alpha potently promoted naive CD4(+) T cells to differentiate into Th9 cells in vitro. Furthermore, the addition of TNF-alpha during Th9 cell differentiation increased T cell survival and proliferation. More importantly, the adoptive transfer of TNF-alpha-treated Th9 cells induced more potent antitumor effects than regular Th9 cells in mouse tumor model. TNF-alpha signals via two cell surface receptors, TNFR1 and TNFR2. Mechanistic studies revealed that TNF-alpha drove Th9 cell differentiation through TNFR2 but not TNFR1. In addition, under Th9 polarizing condition, TNF-alpha activated STAT5 and NF-kappaB pathways in T cells in a TNFR2-dependent manner. Inhibition of STAT5 and NF-kappaB pathways by their specific inhibitors impaired TNF-alpha-induced Th9 cell differentiation. Our results identified TNF-alpha as a new powerful inducer of Th9 cells and clarified the molecular mechanisms underlying TNF-alpha-induced Th9 cell differentiation. |
