Fig. 10

Schematic representation of the proposed mechanism of CRA-induced antitumor antibodies. CRA interacts with the IL-6R to trigger STAT3 pathways for IL-21 production in T cells. STAT3 signaling also leads to the upregulation of c-MAF and BCL-6 transcription factors, which then orchestrate a transcriptional program that upregulates genes encoding IL-21. CRA-induced IL-21 in T cells acts on naive B cells in conjunction with co-stimulatory signals to drive the differentiation of plasma cells subsequent to isotype switching and affinity maturation. IL-21 also upregulated BLIMP1 and then promoted the differentiation of plasma cells