| First Author | Kumar V | Year | 2017 |
| Journal | Cancer Cell | Volume | 32 |
| Issue | 5 | Pages | 654-668.e5 |
| PubMed ID | 29136508 | Mgi Jnum | J:248839 |
| Mgi Id | MGI:6093774 | Doi | 10.1016/j.ccell.2017.10.005 |
| Citation | Kumar V, et al. (2017) Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors. Cancer Cell 32(5):654-668.e5 |
| abstractText | Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects. |
