Fig. 2
From: Targeting oral tumor microenvironment for effective therapy
OSCC cells, CAFs, and also resident macrophages in TME release some factors such as CCL2, CXCR4, CXCL12, and ICAM-1, which lead to the recruitment of monocytes into the tumor. On the other hand, the release of IL-1, IL-6, IL-8, Gas6, IL-4, IL-10, IL-13, and TGF-β by OSCC cells, CAFs and TAMs stimulates the polarization of monocytes and alternative M1 macrophages toward TAMs. TAMs exhaust the anticancer activity of CD8 + T lymphocytes by releasing immune checkpoints like PD-L1. TAMs also stimulate the proliferation of OSCC cells by releasing EGF and CCL18. These molecules can inhibit apoptosis signaling pathways in OSCC cells. (ARG: Arginase-I; Casp: Caspase; CCR2: C-C Motif Chemokine Receptor 2; CCL-2: C-C Motif Chemokine Ligand 2; CSF-1: Colony-stimulating factor-1; CXCL12: C-X-C motif chemokine ligand 12; CXCR4: C-X-C chemokine receptor type 4; CytC: Cytochrome C; EGF: Epidermal growth factor; EGFR: Epidermal growth factor receptor; ICAM-1: Intercellular adhesion molecule-1; Gas6: Growth arrest-specific 6; GM-CSF: Granulocyte-macrophage colony-stimulating factor; TAM: Tumor-associated macrophage; TGF-β: Transforming growth factor-β; OSCC: Oral Squamous Cell Carcinoma; PD-1: Programmed death 1; PD-L1: Programmed death ligand 1; PI3K: Phosphoinositide 3-kinase; STAT: Signal transducer and activator of transcription)