Fig. 3
From: Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends
Transcriptional regulation of dendritic cells (DCs) and exhausted T cells (TEX). a Cell phagocytosis is triggered and results in phagosomal degradation in the cytoplasm of DC cells. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling is activated and releasing type I interferons (IFNs), mainly comprised of IFN-α and IFN-β. Antigens processed are loaded onto MHCs, which subsequently promote the activation of Th1 cells and CTL cells. IFN-γ released by these activated T cells will stimulate the non-canonical NF-κB pathway and release IL-12. Mature immunoregulatory DCs (mDCreg) produces IL-4 and inhibits the functions of cDCs and Th1 cells. b Transcriptional regulation of TEX cells. T cell receptor (TCR) responsive network of transcription factors, including the nuclear factor of activated T cells, cytoplasmic component 1 (NFATC1), thymocyte selection-associated high mobility group box protein (TOX), and B lymphocyte-induced maturation protein 1 (BLIMP1) are overexpressed in TEX cells. NFATC1 and TOX promote the expression of PD-1 (encoded by Pdcd1) and LAG-3 (encoded by Lag3). Highly expressed BLIMP1 induces granzyme B (Gzmb) expression and represses TCF1 expression. Furthermore, TOX induces eomesodermin homologue (EOMES) and nuclear receptor subfamily 4 group A (NR4A) expressions. All of them can inhibit T-bet, which results in the decrease of IFN-γ releasing. IRF4 interferon regulatory factor 4; BATF basic leucine zipper transcriptional factor ATF-like
