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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Expert Opin Ther Targets. 2017 Dec 10;22(1):9–17. doi: 10.1080/14728222.2018.1413091

Figure 1. GTPase and NAD signaling mediated immune suppression mechanisms.

Figure 1

Tumors thrive in a milieu of different types of cells including fibroblasts and collagen. Tumor stromal cells regulate the function of several types of immune cells such as Tregs, TH17, macrophages and MDSCs. Mutant ras promotes canonical RAF-MAPK-ERK-MEK pathway and also activates the Rho GTPase effector protein PAK4. RAF and PAK4 regulate the expression of pro-pro-survival signaling molecules that directly promote immune checkpoint protein PD-1 activation. PD-1 in turn block proper activation of immune surveillance molecules. NAMPT, a rate limiting enzyme in NADPH turnover, can directly activate PD-1 expression.