Immunogenomic landscape of gynecologic carcinosarcoma.

Abstract:

OBJECTIVE:Carcinosarcoma (CS) of the uterus or ovary is a rare, biphasic tumor comprising epithelial and mesenchymal elements, and exhibits more aggressive clinical features than its carcinoma counterpart. Four molecular subtypes of CS were recently established based on genomic aberration profiles (POLE, MSI, CNH, and CNL) and shown to be associated with multiple clinicopathological parameters, including patient outcomes. However, the role of the immune microenvironment in CS remains unclear. Here, we investigated the influence of the immune cells that infiltrate CS to better understand the immunological status of gynecological CS. METHODS:Tumor immune microenvironmental analyses on CS samples were performed using immune cell profiling with RNA-seq, transcriptomic subtyping with microenvironmental genes, and T-cell receptor repertoire assay. Carcinoma and sarcoma elements from CS samples were also assessed separately. RESULTS:Relying on estimations of tumor-infiltrating cell types from RNA-seq data, POLE and MSI (hypermutator) tumors showed an enrichment of M1 macrophages, plasma cells and CD8+ T cells, whereas CNH and CNL (non-hypermutator) tumors had high levels of M2 macrophages. Further subclassification by immune-related, non-cancer genes identified a fraction of tumors with distinct patient outcomes, particularly those with the CNH genomic aberration subtype. T-cell heterogeneity was independently correlated with prolonged progression-free survival. Differential analysis of carcinoma and sarcoma elements identified many shared mutations but there was little overlap in the T-cell receptor repertoire between the two elements. CONCLUSIONS:Tumor immune microenvironmental analyses could offer potential clinical utility in the stratification of gynecological CS above classification by genomic aberration subtype alone.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Gotoh O,Kiyotani K,Chiba T,Sugiyama Y,Takazawa Y,Nemoto K,Kato K,Tanaka N,Nomura H,Hasegawa K,Fujiwara K,Takamatsu S,Matsumura N,Noda T,Mori S

doi

10.1016/j.ygyno.2020.11.030

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

547-556

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(20)34158-5

journal_volume

160

pub_type

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