Immune cytolytic activity is associated with reduced intra-tumoral genetic heterogeneity and with better clinical outcomes in triple negative breast cancer.
Breast cancer
CYT
TNBC
cytolytic activity
heterogeneity
immune cells
immune checkpoint inhibitor
mutation
transcriptome
Journal
American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
03
2021
accepted:
14
04
2021
entrez:
6
8
2021
pubmed:
7
8
2021
medline:
7
8
2021
Statut:
epublish
Résumé
Evaluation of the functional aspects if the tumor immune microenvironment (TIME), such as the recently introduced cytolytic activity score (CYT) index have been under the spotlight in cancer research; however, clinical relevance of immune cell killing activity in breast cancer has never been analyzed in large patient cohorts. We hypothesized that CYT reflects the immune activity of TIME and can predict patient survival. A total of 7533 breast cancer patients were analyzed as both discovery and validation cohorts. We found that high CYT was associated with advanced histological grade and triple-negative breast cancer (TNBC). High CYT in tumors was significantly associated with better survival in TNBC, but unexpectedly, not in other breast cancer subtypes. High CYT TNBC included both favorable immune-related, as well as unfavorable (suppressive) inflammation-related gene sets, and characterized by high infiltration with T cells and B cells. High CYT TNBC was associated with high homologous recombination deficiency and low somatic copy number alteration score and less mutant allele tumor heterogeneity, but not with tumor mutation burden (TMB). Although CYT was not associated with pathological complete response after neoadjuvant chemotherapy, it was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, CYT of TNBC is associated with enhanced anti-cancer immunity, less intra-tumoral heterogeneity, and with better survival.
Types de publication
Journal Article
Langues
eng
Pagination
3628-3644Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232097
Pays : United States
Informations de copyright
AJCR Copyright © 2021.
Déclaration de conflit d'intérêts
None.
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