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Immune mechanisms shape the clonal landscape during early progression of prostate cancer

ABSTRACT: Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Here we show that two types of tumor clonal landscapes emerge during early progression of prostate cancer in genetically-engineered mouse models. Using lineage tracing and single-cell transcriptomics, we find that slowly progressing tumors contain a multiclonal landscape of relatively homogenous subpopulations within a well-organized tumor microenvironment, whereas more advanced and aggressive tumors contain competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that the dominant/minor modality is associated with differential immunoediting, in which minor clones are marked by increased expression of IFNγ-response genes and the T-cell activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNγ pathway can rescue minor clones from elimination. These findings suggest new immunotherapy approaches to modulate clonal fitness and tumor progression in prostate cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE196371 | GEO | 2023/04/01

REPOSITORIES: GEO

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