| First Author | Chmielewski M | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 11 | Pages | 3205-3219 |
| PubMed ID | 29241547 | Mgi Jnum | J:254790 |
| Mgi Id | MGI:6103936 | Doi | 10.1016/j.celrep.2017.11.063 |
| Citation | Chmielewski M, et al. (2017) CAR T Cells Releasing IL-18 Convert to T-Bet(high) FoxO1(low) Effectors that Exhibit Augmented Activity against Advanced Solid Tumors. Cell Rep 21(11):3205-3219 |
| abstractText | Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bet(high) FoxO1(low) effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206(-) M1 macrophages and NKG2D(+) NK cells increased in number, whereas Tregs, suppressive CD103(+) DCs, and M2 macrophages decreased, suggesting that "iIL18 TRUCKs" can be used to sensitize large solid tumor lesions for successful immune destruction. |
