| First Author | Morales Del Valle C | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 5 | Pages | 1434-1445.e3 |
| PubMed ID | 31042471 | Mgi Jnum | J:281865 |
| Mgi Id | MGI:6380808 | Doi | 10.1016/j.celrep.2019.04.016 |
| Citation | Morales Del Valle C, et al. (2019) Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism. Cell Rep 27(5):1434-1445.e3 |
| abstractText | Chronic exposure to tumor-associated antigens inactivates cognate T cells, restricting the repertoire of tumor-specific effector T cells. This problem was studied here by transferring TCR transgenic CD4 T cells into recipient mice that constitutively express a cognate self-antigen linked to MHC II on CD11c-bearing cells. Immunotherapeutic agonists to CD134 plus CD137, "dual costimulation," induces specific CD4 T cell expansion and expression of the receptor for the Th2-associated IL-1 family cytokine IL-33. Rather than producing IL-4, however, they express the tumoricidal Th1 cytokine IFNgamma when stimulated with IL-33 or IL-36 (a related IL-1 family member) plus IL-12 or IL-2. IL-36, which is induced within B16-F10 melanomas by dual costimulation, reduces tumor growth when injected intratumorally as a monotherapy and boosts the efficacy of tumor-nonspecific dual costimulated CD4 T cells. Dual costimulation thus enables chronic antigen-exposed CD4 T cells, regardless of tumor specificity, to elaborate tumoricidal function in response to tumor-associated cytokines. |
