Highlights
- •Tumor immune microenvironment signalling influences tumor progression.
- •Tumor associated macrophages are characterized by a dual pro- and anti-tumor activity.
- •Tumor associated macrophages emerge as a potential target for cancer treatment in gastric cancer.
Abstract
Graphical abstract

Keywords
The role of microenvironment in GC development and progression
Tumor-Associated Macrophage in solid tumors
The dual role of TAMs: M2 macrophages and cancer development and progression

TAMs and immune response
Inflammation, microenvironment and TAMs in GC development
Limitations of the current evidence on TAMs
TAMs as a potential target for cancer treatment
Direct inhibition of TAM
Class of drug | Drug | Target | Compound characteristics | Clinical trial | Tumor Type | Trial design | Treatment |
---|---|---|---|---|---|---|---|
Monoclonal antibodies | Emactuzumab (RG7155) | CSF1R | Mactuzumab binds to CSF1R expressed on macrophages and inhibits binding of colony-stimulating factor-1 (CSF-1) to CSF1R. | NCT02323191 NCT02760797 NCT02923739 NCT03369964 NCT03821246 NCT01494688 NCT03193190 | Locally advanced or metastatic solid tumors | Phase I Phase I Phase II Phase I Pahse II Phase I Phase I | Single agent Single agent Paclitaxel Bevacizumab Anti CD20. Enzalutatmide + Atezolizumab. Paclitaxel. Multiple immunotherapy |
Cabiralizumab (FPA008) | Binds to CSF1R expressed on monocytes, macrophages, and osteoclasts and inhibits CSF1R ligands colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34), from binding to CSF1R | NCT02526017 NCT03336216 NCT03768531 NCT03335540 | Advanced Solid Tumors, Including But Not Limited to Lung Cancer Head and Neck Cancer Pancreatic Cancer Ovarian Cancer Renal Cell Carcinoma Malignant Glioma Biliary tract | Phase I Phase I Phase I Phase I | Nivolumab. Nivolumab ±CT. Single agent. Multiple immunotherapy | ||
IMC-CS4 | Bactuzumab binds to CSF1R expressed on macrophages and inhibits binding of colony-stimulating factor-1 (CSF-1) to CSF1R. | NCT01346358 NCT03153410 NCT02265536 | Advanced solid tumors refractory to standard therapy, Pancreatic cancer, Breast Cancer, Prostate Cancer | Phase I Phase I Phase I | Single agent CY, Pembrolizumab, GVAX Single agent | ||
Tyrosine Kinase inhibitors | Pexidartinib (PLX3397) | CSF1R, cKIT, FLT3, PDGFR | Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3 | NCT02584647 NCT02071940 NCT02452424 NCT01499043 NCT01349036 NCT01596751 NCT01525602 | Advanced solid tumors refractory to standard therapy, Sarcoma, Melanoma, Melanoma Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Gastrointestinal Stromal Tumor (GIST) Ovarian Cancer | Phase I Phase I Phase I Phase I Phase II Phase Ib/II Phase I | Single agent Single Agent Combined with Pembrolizumab Single Agent Single Agent Combined with Eribulin Single Agent |
ARRY-382, | CSF-1R | A small molecule and orally available inhibitor of CSF-1 | NCT01316822 | Advanced solid tumors refractory to standard therapy | Phase I | Single agent | |
PLX7486 | CSF-1R, TRKA-B-C | The tosylate salt form of PLX7486, a selective inhibitor of the receptor tyrosine kinases colony-stimulating factor-1 receptor (CSF1R; fms) and neurotrophic tyrosine kinase receptor types 1, 2 and 3 (TrkA, TrkB, and TrkC, respectively) | NCT01804530 | Advanced solid tumors refractory to standard therapy | Phase I | Single agent | |
BLZ945 | CSF-1R | BLZ945 selectively binds to CSF1R expressed on tumor-associated macrophages (TAMs), blocks CSF1R activity, and inhibits CSF1R-mediated signal transduction pathways. | NCT02829723 | Advanced solid tumors refractory to standard therapy | Phase I/II | Combined with PDR001 | |
JNJ- 40,346,527 | CSF-1R | A small molecule, orally available inhibitor of colony-stimulating factor-1 receptor (CSF1R; FMS) with potential antineoplastic activity. FMS tyrosine kinase inhibitor JNJ-40346527 blocks the receptor-ligand interaction between FMS and its ligand CSF1 | NCT03177460 NCT01054014 | Advanced solid tumors refractory to standard therapy, Prostate | Phase I Phase I | versus Daratumumab. Single agent |
Indirect inhibition of TAM
Conclusion
Funding
Declaration of Competing Interest
Acknowledgements
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