Fig. 3
From: Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma
The mechanisms of Treg inhibit Tconv through APC. Treg and Tconv contact directly with the same APC and establish tumor specific suppressive TME. a: Treg capture and degradate CD86 on DC with CTLA4, the process occurs in LN/TLS and PanIN, activating Treg migrate to established tumor and transform to resting Treg and execute suppression; b: Treg (also Tconv) contact with APC through various pairs of ligand-receptor including of TCR/MHC, CD28/CD86, CD28/CD80, CTLA4/CD86, CTLA4/CD80, mature DC dominantly express high level of CD86 and combine with CD28 and CTLA4, MDSC preferentially express CD80 and combine with CTLA4, immature/inducible DC express both CD86 and CD80. Notably, MDSC express low level of MHC and enhance suppressive function of Treg with weak TCR signal, whereas DC express high level of MHC and promote Treg activation and proliferation; c: APC could transform each other with the effect of Treg and Tconv concordantly; d: APC inhibit Tconv through several soluble factors and induce Tconv anergy through weak/downregulating TCR signal; e: APC inhibit CD4+ Tconv directly and CD8+ Tconv indirectly mainly by downregulating IL-2 and IFN-γ et al., Treg cells could inhibit Tconv by depriving IL-2. Biophysical stability of CTLA4/CD28-CD80/CD86 polymer: CTLA4-CD80 > CTLA4-CD86 > CD28-CD86 > CD28- CD80