Immune cells and signatures characterize tumor microenvironment and predict outcome in ovarian and endometrial cancers

Immunotherapy. 2021 Oct;13(14):1179-1192. doi: 10.2217/imt-2021-0052. Epub 2021 Aug 23.

Abstract

Aims: We investigated immunogenomic signatures and correlated them with survival in ovarian cancer (OV) and endometrial cancer (EC). Materials & method: We used whole transcriptome sequencing data from uterine serous cancer and The Cancer Genome Atlas data of OV and EC (n = 719). Gene expression score was calculated. Population abundance of immune cells were estimated. Results: TGF-β, myeloid cells, IFN-γ, T cells, B cells and endothelial cells predicted overall survival. Whereas CD47, neutrophils and endothelial cells predicted progression-free survival. In multivariate analyses, TGF-β, CD47 and monocytic cells predicted survival in high levels of microsatellite instability (MSI-H) EC whereas high IFN-γ trended toward improved survival in the MSI-S EC. High IFN-γ/low TGF-β and high IFN-γ/low CD47 signatures predicted longer overall survival. Low TGF-β/low CD47 signature predicted longer overall survival only in the MSI-H EC. Conclusion: Our data support the role of immune markers in predicting survival in OV/EC.

Keywords: CD47; MSI-H; T cells; TGF-β; immune cells; immune signatures; ovarian and endometrial cancers; survival; tumor-associated myeloid cells.

Plain language summary

Lay abstract We studied the association of immune markers and immune cells with survival outcome in ovarian and endometrial cancers. We performed gene expression analyses on tumor tissue of 719 patients. We generated signatures for the immune cells and markers and correlated them with survival outcome. We showed that specific immune cells and markers correlated strongly with survival even after we adjusted for other confounding factors. Further, we showed that these immune markers and immune cells have different correlation with survival when stratified in subtypes of endometrial cancer. Our data support the role of these immune markers in predicting survival outcome in ovarian and endometrial cancers.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / immunology*
  • Endometrial Neoplasms / immunology*
  • Exome Sequencing
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Ovarian Neoplasms / immunology*
  • Retrospective Studies
  • Transcriptome / immunology*
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor