Figure 1.

Therapeutic strategies for TME-directed therapy. (A) Targeting TAMs: (1) Anti-CCL2: Monoclonal antibody Carlumab, CCL2 antagonist PF04136309, (2) Anti-CSF1R: Monoclonal Antibody Emactuzumab, tyrosine kinase inhibitor Pexidartinib, (3) TLR agonists: small molecules imiquimod, motolimod, SD-101, (4) CD40 agonists: Monoclonal Antibodies Selicrelumab and CDX-1140, PI3Kγ inhibitor: IPI-549. (B) Targeting MDSCs: (1) IDO inhibitors: Epacadostat, Navoximod, BMS-986205, (2) Anti-CSF1R: Monoclonal Antibody Emactuzumab, tyrosine kinase inhibitor Pexidartinib, (3) CXCR2 inhibitor: SX-682 (4) PDE5 inhibitor tadalafil, (5) STAT3 inhibitor C188-9. (C) Targeting Tregs: (1) GITR agonists: Monoclonal Antibodies MEDI1873 and REGN6569, (2) OX40 agonists: Monoclonal Antibodies MEDI0562, MEDI6469, MEDI6383 and INBRX-106, (3) FOXP3 inhibitor: AZD8701, (4) Anti-CD25: Monoclonal Antibody Daclizumab, (5) Anti-CTLA-4: Monoclonal Antibodies Ipilimumab and Tremelimumab, (6) Anti-CD73: Monoclonal Antbody Oleclumab, (7) Anti-CCR4: Monoclonal Antibody Mogamulizumab. (D) Targeting CAFs: (1) Anti-FAP: Monoclonal Antibodies Sibrotuzumab and RO6874281, (2) STAT3 inhibitor: C188-9, (3) JAK2 inhibitor: Ruxolitinib, (4) Anti-IL-6: Monoclonal Antibody Siltuximab, (5) Anti-MMP: small molecule S-3304. Abbreviations: CAFs = Cancer Associated Fibroblasts, CCR4 = C-C Motif Chemokine Receptor 4,CD73 = Cluster of Differentiation 73, CD40 = Cluster of differentiation 40, CSF1R = Colony stimulating factor, receptor, CTLA-4 = Cytotoxic T Lymphocyte-Associated protein 4,FAP = Fibroblast Activation Protein, FOXP3 = Forkhead box P3, GITR = Glucocorticoid-Induced TNFR-related protein, IDO1 = Indoleamine 2,3-dioxygenase 1, JAK2 = Janus Kinase 2, MDSCs = Myeloid-Derived Suppressor cells, PDE5 = Phosphodiesterase 5, PI3Kγ = Phosphoinositide 3-Kinase γ, STAT3 = Signal transducer and activator of transcription 3, TAMs = Tumor Associated Macrophages, TLR = Toll-like Receptor, Tregs = T regulatory cells.