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. 2020 Apr 28;11:676. doi: 10.3389/fimmu.2020.00676

FIGURE 1.

FIGURE 1

Treg cell generation in lung cancer. (A) Ex vivo generation of Tregs is modulated by the first and second signaling of T cell activation in lung cancer. In brief, neoantigens determines the TCR repertoire of Tregs (left) and CTLA-4-CD80/CD86 crosslink downregulates NF-κB activity, which was reported to inhibit Foxp3 expression by upregulating miR-34a, finally promoting Treg cell polarization. (B-C) APC- or tumor cell-derived PD-L1 or TGF-β can also induce Treg cell generation by interaction their corresponding receptors, respectively, on TILs via diverse mechanisms. On the one hand, TGF-β induces CTLA-4 expression on TILs, on the other hand, TGF-mediated activation of Smad and ERK1/2 can enhance Foxp3 expression in Treg cells. Moreover, TGF-β inhibits LSD1-Gfi-1 axis via an unknown mechanism to enhance immunosuppressive CD103+ Treg differentiation. (D) IL-10 induced Foxo1 translocation into nucleus facilities its occupation in Foxp3 promoter upon STAT3 activation and PI3K-Akt inactivation.