Intratumoral heterogeneity and clonal evolution in liver cancer

Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature communications 2020-01, Vol.11 (1), p.291-291, Article 291
Hauptverfasser: Losic, Bojan, Craig, Amanda J., Villacorta-Martin, Carlos, Martins-Filho, Sebastiao N., Akers, Nicholas, Chen, Xintong, Ahsen, Mehmet E., von Felden, Johann, Labgaa, Ismail, DʹAvola, Delia, Allette, Kimaada, Lira, Sergio A., Furtado, Glaucia C., Garcia-Lezana, Teresa, Restrepo, Paula, Stueck, Ashley, Ward, Stephen C., Fiel, Maria I., Hiotis, Spiros P., Gunasekaran, Ganesh, Sia, Daniela, Schadt, Eric E., Sebra, Robert, Schwartz, Myron, Llovet, Josep M., Thung, Swan, Stolovitzky, Gustavo, Villanueva, Augusto
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution. Immune-mediated selection pressures impact the clonal evolution of tumours. Here, in hepatocellular carcinoma the authors map spatio-temporal interactions between tumor and immune cells, highlighting the regulatory substrate of intra-tumoural heterogeneity that correlates with regional adaptive immune responses.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-14050-z