| First Author | Herrmann A | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 19 | Pages | 7455-64 |
| PubMed ID | 20841481 | Mgi Jnum | J:164674 |
| Mgi Id | MGI:4834953 | Doi | 10.1158/0008-5472.CAN-10-0736 |
| Citation | Herrmann A, et al. (2010) Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells. Cancer Res 70(19):7455-64 |
| abstractText | Improving effector T-cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Signal transducer and activator of transcription 3 (Stat3) in the myeloid compartment constrains Th1-type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo small interfering RNA (siRNA) delivery platform by conjugating a Toll-like receptor 9 agonist with siRNA that efficiently targets myeloid and B cells. Here, we show that either CpG triggering combined with the genetic Stat3 ablation in myeloid/B cell compartments or administration of the CpG-Stat3siRNA drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we show that both approaches are capable of increasing dendritic cell and CD8(+) T-cell engagement in tumor-draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8(+) T cells in vivo, upregulating effector molecules such as perforin, granzyme B, and IFN-gamma. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T-cell therapies. |
