Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

Figure 3

Differences in the immune responses to tumor induced by IL-12 and IL-23 and their molecular mechanisms in tumor microenvironments. STAT3 activation induces IL-23 expression, which is mainly observed in TAMs, via direct transcriptional activation of the IL-23p19 gene together with NF-𝜅B/RelA(p65). On the other hand, STAT3 activation inhibits NF-𝜅B/c-Rel-dependent IL-12p35 gene expression in tumor-associated DCs, possibly through the STAT3-dependent induction of the ETS transcriptional suppressor ETV3 and the helicase family corepressor SBNO2. Thus, STAT3 promotes IL-23-mediated protumor immune responses while inhibiting IL-12-dependent antitumor immunity.