| First Author | Tshering LF | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 12 | Pages | 1071-1086.e8 |
| PubMed ID | 37148881 | Mgi Jnum | J:337538 |
| Mgi Id | MGI:7495413 | Doi | 10.1016/j.devcel.2023.04.010 |
| Citation | Tshering LF, et al. (2023) Immune mechanisms shape the clonal landscape during early progression of prostate cancer. Dev Cell 58(12):1071-1086.e8 |
| abstractText | Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Using multicolor lineage tracing in genetically engineered mouse models and single-cell transcriptomics, we show that slowly progressing tumors contain a multiclonal landscape of relatively homogeneous subpopulations within a well-organized tumor microenvironment. In more advanced and aggressive tumors, however, the multiclonal landscape develops into competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that this dominant/minor landscape is associated with differential immunoediting, in which minor clones are marked by an increased expression of IFNgamma-response genes and the T cell-activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNgamma pathway can rescue minor clones from elimination. Notably, the immune-specific gene signature of minor clones exhibits a prognostic value for biochemical recurrence-free survival in human prostate cancer. These findings suggest new immunotherapy approaches for modulating clonal fitness and tumor progression in prostate cancer. |
