Serum CD95L level correlates with tumor immune infiltration and is a positive prognostic marker for advanced high grade serous ovarian cancer

Abstract : 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. Immunohistochemical 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 HGSOC patients 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 (<516 pg/mL, hazard ratio (HR), 3.54; 95% confidence interval (CI), 1.13-11.11), and < 1200 activated CD8+ (Granzyme B+) cells (HR, 2.63; 95% CI, 1.16-5.95) were independent poor prognostic factors for recurrence, whereas >6000 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+, but also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker. Implications Serum s-CD95L is correlated with the number of tumor-infiltrating immune cells in HGSOC and could be used as a non-invasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment.
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Submitted on : Thursday, October 3, 2019 - 2:52:11 PM
Last modification on : Friday, November 15, 2019 - 4:28:25 PM

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Thibault de la Motte Rouge, Julien Corne, Aurelie Cauchois, Marie Le Boulch, Clotilde Poupon, et al.. Serum CD95L level correlates with tumor immune infiltration and is a positive prognostic marker for advanced high grade serous ovarian cancer. Molecular Cancer Research, American Association for Cancer Research, 2019, ⟨10.1158/1541-7786.MCR-19-0449⟩. ⟨hal-02304765⟩

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