Regulation of the innate and adaptive immune responses

by Stat-3 signaling in tumor cells

Speaker: 陳宇楓

Commentator: 蘇五洲 醫師

Room: 601教室

Date: 2004,2,18 15:00-16:00

Abstract:

   Although the developing of invasive, metastatic cancer would activate inflammatory responses, the immune system generally ignores and tolerates disseminated tumors. The rules governing such mechanisms in which the elicitation of immune responses were blocked by the progression of tumors remains unclear. The signal transducers and activators of transcription (STATs), originally discovered as intracellular effectors of normal signaling pathways induced by cytokines, were shown to participate in the formation of tumors by stimulating cell proliferation and preventing apoptosis in recent studies¹. In this paper, the authors investigate the expression of proinflammatory cytokines and chemokines by blocking Stat-3 in tumor cells. In addition, dentritic cells only become fully activated with proper inflammatory signals; they try to find out the factors involved in inhibiting the maturation of dentritic cells. By blocking Stat-3 signaling in the B16 tumors in vivo with Stat-3b gene, T cell infiltration can be observed in local tumors. Meanwhile, higher TRP2-specific IFN-g production was seen in splenocytes from mice injected with irradiated Stat-3b-transfected B16 cells. Their result has revealed significance in the implication of therapeutic values. Interrupting Stat-3 signaling with selective inhibitors would not only have direct anti-tumor effects through growth suppression and apoptosis induction, but also activate the cross talks between the innate and adaptive immunity.

References:

1.     Bromberg, J.F. et al. Stat-3 as an oncogene. Cell 98, 295-303 (1999).

2.     Tianhong, W. et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nature medicine 10, 48-54 (2004).