Serum CD95L Level Correlates with Tumor Immune Infiltration and Is a Positive Prognostic Marker for Advanced High-Grade Serous Ovarian Cancer

摘要

Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels >= 516 pg/mL showed increased infiltration by CD3(+) T cells (P = 0.001), comprising both cytotoxic CD8(+) (P = 0.01) and CD4(+) (P = 0.0062) cells including FoxP3(+) regulatory T cells (P = 0.0044). Also, the number of tumor-infiltrating CD20(+) B cells (P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [ 6,000 CD3(+) cells (HR, 0.34; 95% CI, 0.15-0.79) was a good prognostic factor. Thus, low levels of s-CD95L (<516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3(+) and CD8(+), and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker.