| First Author | Zhang L | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 4300 |
| PubMed ID | 34262035 | Mgi Jnum | J:344752 |
| Mgi Id | MGI:6725665 | Doi | 10.1038/s41467-021-24610-x |
| Citation | Zhang L, et al. (2021) Loss of fragile site-associated tumor suppressor promotes antitumor immunity via macrophage polarization. Nat Commun 12(1):4300 |
| abstractText | Common fragile sites (CFSs) are specific breakage-prone genomic regions and are present frequently in cancer cells. The (E2-independent) E3 ubiquitin-conjugating enzyme FATS (fragile site-associated tumor suppressor) has antitumor activity in cancer cells, but the function of FATS in immune cells is unknown. Here, we report a function of FATS in tumor development via regulation of tumor immunity. Fats(-/-) mice show reduced subcutaneous B16 melanoma and H7 pancreatic tumor growth compared with WT controls. The reduced tumor growth in Fats(-/-) mice is macrophage dependent and is associated with a phenotypic shift of macrophages within the tumor from tumor-promoting M2-like to antitumor M1-like macrophages. In addition, FATS deficiency promotes M1 polarization by stimulating and prolonging NF-kappaB activation by disrupting NF-kappaB/IkappaBalpha negative feedback loops and indirectly enhances both CD4(+) T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) adaptive immune responses to promote tumor regression. Notably, transfer of Fats(-/-) macrophages protects mice against B16 melanoma. Together, these data suggest that FATS functions as an immune regulator and is a potential target in cancer immunotherapy. |
