High Tumor-Infiltrating Lymphocyte Count Is Associated with Distinct Gene Expression Profile and Longer Patient Survival in Advanced Ovarian Cancer

Abstract

Cancer-related immunity plays a significant role in the outcome of ovarian cancer, but the exact mechanisms are not fully explored. A retrospective, real-life observational study was conducted including 57 advanced ovarian cancer patients. Immunohistochemistry for CD4+, CD8+, and CD45+ was used for assessing tumor-infiltrating immune cells. Furthermore, an immune-related gene expression assay was performed on 12–10 samples from patients with less than and more than 1-year overall survival (OS), respectively. A higher number of CD4+ (p = 0.0028) and CD45+ (p = 0.0221) immune cells within the tumor microenvironment were associated with longer OS of patients. In a multivariate setting, higher CD4+ T cell infiltration predicted longer OS (p = 0.0392). Twenty-three differentially expressed genes—involved in antigen presentation, costimulatory signaling, matrix remodeling, metastasis formation, and myeloid cell activity—were found when comparing the prognostic groups. It was found that tumor-infiltrating immune cell counts are associated with peculiar gene expression patterns and bear prognostic information in ovarian cancer. SOX11 expression emerged and was validated as a predictive marker for OS.

Keywords

• ovarian neoplasms
• immunohistochemistry
• NanoString
• CD4-positive T-lymphocytes
• CD8-positive T-lymphocytes
• CD45-positive leukocytes