Impact of immune infiltration signatures on prognosis in endometrial carcinoma is dependent on the underlying molecular subtype Journal Article

   

Authors:	Dessources, K.; Ferrando, L.; Zhou, Q. C.; Iasonos, A.; Abu-Rustum, N. R.; Reis-Filho, J. S.; Riaz, N.; Zamarin, D.; Weigelt, B.
Article Title:	Impact of immune infiltration signatures on prognosis in endometrial carcinoma is dependent on the underlying molecular subtype
Abstract:	Objectives: Increased numbers of tumor infiltrating lymphocytes (TIL) in endometrial cancer (EC) are associated with improved survival, but it is unclear how this prognostic significance relates to the underlying EC molecular subtype. In this explorative hypothesis-generating study, we sought to define the immune signatures associated with the molecular subtypes of EC (i.e., POLE-mutated, microsatellite unstable (MSI-high), copy number (CN)-low, and CN-high) and to determine their correlation with patient outcomes. Methods: RNA-sequencing and molecular subtype data of 232 primary ECs were obtained from The Cancer Genome Atlas. Deconvolution of bulk gene expression data was performed using single sample Gene Set Enrichment Analysis (ssGSEA) and Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT). The association of the resultant immune signatures with overall survival was determined across molecular subtypes. Results: Statistically significant differences in enrichment were identified in 16/30 and 6/23 immune gene sets by ssGSEA and CIBERSORT, respectively. Signature of CD8+ cells in ECs of CN-high molecular subtype was associated with improved overall survival by ssGSEA (p = 0.0108), while CD8 signatures did not appear to be prognostic in MSI-high (p = 0.74) or CN-low EC molecular subtypes (p = 0.793). Of all molecular subtypes, CN-high ECs exhibited the lowest levels of CD8+ T cell infiltration. Consistent with antigen-induced T cell activation and exhaustion, enrichment for immunomodulatory receptors was predominantly observed in ECs of MSI-high and POLE-mutated molecular subtypes. Conclusions: Deconvolution of bulk gene expression data can be used to identify populations of immune infiltrated endometrial cancers with improved survival. These data support the existence of unique mechanisms of immune resistance within molecular subgroups of the disease. © 2023 Elsevier Inc.
Keywords:	adult; cancer survival; controlled study; aged; human cell; major clinical study; overall survival; outcome assessment; endometrial cancer; endometrium carcinoma; endometrial neoplasms; cd8 antigen; cd8+ t lymphocyte; cd8-positive t-lymphocytes; gene expression; cell infiltration; genetic transcription; pathology; angiogenesis; microsatellite dna; rna; endometrium tumor; t lymphocyte activation; microsatellite repeats; molecular subtype; exhaustion; cancer prognosis; deconvolution; immune infiltration; humans; prognosis; human; female; article; rna sequencing; rna-sequencing; gene set enrichment analysis
Journal Title:	Gynecologic Oncology
Volume:	171
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2023-04-01
Start Page:	15
End Page:	22
Language:	English
DOI:	10.1016/j.ygyno.2023.01.037
PUBMED:	36804617
PROVIDER:	scopus
PMCID:	PMC10040428
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85148700650&doi=10.1016%2fj.ygyno.2023.01.037&partnerID=40&md5=66179ddebf86895b124ad84d5615596e
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Dmitriy Zamarin and Britta Weigelt -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/204342