Genomic mapping of copy number variations influencing immune response in breast cancer.

Autor: López-Cade, Igor, García-Barberán, Vanesa, Cabañas Morafraile, Esther, Díaz-Tejeiro, Cristina, Saiz-Ladera, Cristina, Sanvicente, Adrián, Pérez Segura, Pedro, Pandiella, Atanasio, Győrffy, Balázs, Ocaña, Alberto
Předmět:
Zdroj: Frontiers in Oncology; 9/1/2022, Vol. 12, p1-11, 11p
Abstrakt: Identification of genomic alterations that influence the immune response within the tumor microenvironment is mandatory in order to identify druggable vulnerabilities. In this article, by interrogating public genomic datasets we describe copy number variations (CNV) present in breast cancer (BC) tumors and corresponding subtypes, associated with different immune populations. We identified regulatory T-cells associated with the Basal-like subtype, and type 2 T-helper cells with HER2 positive and the luminal subtype. Using gene set enrichment analysis (GSEA) for the Type 2 T-helper cells, the most relevant processes included the ERBB2 signaling pathway and the Fibroblast Growth Factor Receptor (FGFR) signaling pathway, and for CD8+ T-cells, cellular response to growth hormone stimulus or the JAK-STAT signaling pathway. Amplification of ERBB2, GRB2, GRB7, and FGF receptor genes strongly correlated with the presence of type 2 T helper cells. Finally, only 8 genes were highly upregulated and present in the cellular membrane: MILR1, ACE, DCSTAMP, SLAMF8, CD160, IL2RA, ICAM2, and SLAMF6. In summary, we described immune populations associated with genomic alterations with different BC subtypes. We observed a clear presence of inhibitory cells, like Tregs or Th2 when specific chromosomic regions were amplified in basal-like or HER2 and luminal groups. Our data support further evaluation of specific therapeutic strategies in specific BC subtypes, like those targeting Tregs in the basal-like subtype. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index