Fig. 3

This figure illustrates the infiltration MDSCs into OSCC and interactions with cancer and anticancer immune cells in TME. The release of some factors such as CCL2, IL-8, CXCL1, M-CSF and CSF-1 by OSCC cells and CAFs stimulates the recruitment of MDSCs into the tumor. The secretions by OSCC can also induce polarization of bone marrow stem cells into MDSCs. MDSCs can exhaust NK cells and CD8 + T cells by expressing CD155 and PD-L1. Furthermore, these secretions stimulate the differentiation of CD4 + T cells into CD4 + Th17 cells while inhibiting differentiation into CD8 + T cells. The release of IFN-γ and TNF-α by NK cells and effector CD8 + T cells can stimulate apoptosis in OSCC. However, MDSCs blunt the anti-tumor activity of these cells by expressing PD-L1 and CD155. The release of growth factors by MDSCs can also inhibit apoptosis in OSCC cells. (ARG: Arginase-I; BMSC: Bone marrow stem cell; Casp: Caspase; CCR2: C-C Motif Chemokine Receptor 2; CCL-2: C-C Motif Chemokine Ligand 2; CSF-1: Colony-stimulating factor-1; CXCL1: C-X-C motif chemokine ligand 1; CytC: Cytochrome C; EGF: Epidermal growth factor; EGFR: Epidermal growth factor receptor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; TGF-β: transforming growth factor-β; TIGIT: T cell immunoreceptor with Ig and ITIM domains; PD-1: Programmed death 1; PD-L1: Programmed death ligand 1; PGE2: Prostaglandin E2; PI3K: Phosphoinositide 3-kinase; M-CSF: Macrophage colony-stimulating factor; STAT: Signal transducer and activator of transcription)