Figure 2.

Proposed mechanism for the immunotherapeutic effects of NF-κB modulating agents. In the absence of treatment, MDSCs and Treg cells actively inhibit CD4⁺ and CD8⁺ Teff cells; tumor-derived Ag presentation by DCs is low. NF-κB inhibitors increase the numbers and activity of Teff cells by decreasing the recruitment and fitness of MDSCs and impairing Treg cell identity, relieving the suppression of Teff cells. Moreover, these treatments reduce PD-L1 expression and induce tumor cell death, leading to enhanced Ag-presentation by DCs. Conversely, stimulation of TNFRSFs and TLRs on DCs and Teff cells activates NF-κB to increase their maturation numbers and function. All these agents potentiate the therapeutic effect of anti-PD-1 mAbs. Some figure elements were obtained from Servier Medical Art (https://smart.servier.com/).