| First Author | Tan IL | Year | 2021 |
| Journal | Oncogene | Volume | 40 |
| Issue | 2 | Pages | 396-407 |
| PubMed ID | 33159168 | Mgi Jnum | J:301477 |
| Mgi Id | MGI:6506078 | Doi | 10.1038/s41388-020-01536-0 |
| Citation | Tan IL, et al. (2021) CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model. Oncogene 40(2):396-407 |
| abstractText | The immune microenvironment of tumors can play a critical role in promoting or inhibiting tumor progression depending on the context. We present evidence that tumor-associated macrophages/microglia (TAMs) can promote tumor progression in the sonic hedgehog subgroup of medulloblastoma (SHH-MB). By combining longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) and immune profiling of a sporadic mouse model of SHH-MB, we found the density of TAMs is higher in the ~50% of tumors that progress to lethal disease. Furthermore, reducing regulatory T cells or eliminating B and T cells in Rag1 mutants does not alter SHH-MB tumor progression. As TAMs are a dominant immune component in tumors and are normally dependent on colony-stimulating factor 1 receptor (CSF1R), we treated mice with a CSF1R inhibitor, PLX5622. Significantly, PLX5622 reduces a subset of TAMs, prolongs mouse survival, and reduces the volume of most tumors within 4 weeks of treatment. Moreover, concomitant with a reduction in TAMs the percentage of infiltrating cytotoxic T cells is increased, indicating a change in the tumor environment. Our studies in an immunocompetent preclinical mouse model demonstrate TAMs can have a functional role in promoting SHH-MB progression. Thus, CSF1R inhibition could have therapeutic potential for a subset of SHH-MB patients. |
