“…Increasing numbers of studies have demonstrated that the upregulation of B7/CD28 family members, such as PD-L1, B7x and HHLA2, is associated with activating EGFR mutations, 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 which may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment (TME). In this review, we will discuss the regulatory effect of EGFR signaling on the B7/CD28 pathways, which may inform future combination therapeutic strategies and overcome the current challenge of EGFR-TKI resistance.…”