Figure 3.

Role of inflammatory transcription factors on tumor development and the mechanism of tumor regression by blocking of NF‐kB or STAT3. (a) Tumor progression state with tumor‐associated inflammation and suppression of antitumor immunity. In tumor cells, STAT3 and NF‐kB are activated via cytokines from myeloid cells and support proliferation and antiapoptosis. This is associated with reduced expression of suppressors of cytokine signaling (SOCS)1 and SOCS3. Reduced STAT1 activation is often associated with highly malignant tumors. In myeloid cells, for growth promoting factor production, NF‐kB, STAT1 and STAT3 usually work positively, while SOCS1 and SOCS3 work negatively. However, in the status of the suppression of antitumor immunity, STAT3 is activated and suppresses NF‐kB and STAT1. Enhanced SOCS1 and reduced SOCS3 expression is associated with this situation. (b) When the NF‐kB pathway is blocked, cytokine production from myeloid cells is blocked and tumor cell apoptosis is accelerated. However, NF‐kB blockage may weaken antitumor immunity. (c) When STAT3 is blocked, tumor cell apoptosis is enhanced and antitumor immunity is reinforced by increasing chemokine production from tumor cells and by enhancing dendritic activation and cytotoxic T cells (CTL) activation. However, this may enhance inflammation which supplies tumor‐promoting factors.