Prognostic value of regulatory T cells and T helper 17 cells in high grade serous ovarian carcinoma

Abstract

Purpose In recent years the tumor microenvironment and its interaction with the tumor has emerged into research focus with increased attention to the composition of Tumor-infiltrating lymphocytes. We wanted to quantify the composition of Regulatory T cells (Tregs) and T helper 17 cells (Th17 cells) and their prognostic impact in high-grade serous tubo-ovarian carcinoma. Methods Tregs and Th17 cells were determined by immunohistochemical analysis of CD25 FoxP3 and RORγt, respectively on tissue microarrays of a cohort of 222 patients with reviewed histology and available clinical data. Expression was analyzed with Qupath for quantification and integration with clinical data enabled calculation of prognostic impact. For validation FOXP3 and RORC mRNA expression levels from 502 patients with HGSC in publicly available datasets were evaluated. Results An average percentage of 0.93 Tregs and of 0.06 Th17 cells was detected per cells in overall tissue. Optimal cut-offs were determined and higher Tregs were associated with a better overall survival in stroma (p = 0.006), tumor area (p = 0.0012) and overall tissue (p = 0.02). After accounting for well-known prognostic factors age at diagnosis, residual tumor and FIGO stage, this association remained significant for stromal Tregs with overall survival (p = 0.02). Survival analysis for Th17 cells revealed no significant association with survival rates. Moreover, lower Th17/Treg ratios had a positive impact on patient overall survival (p = 0.025 tumor, p = 0.049 stroma and p = 0.016 overall tissue). Conclusion Our results outline a positive prognostic effect for higher Tregs but not for Th17 in high grade serous tubo-ovarian carcinoma.

Distinct T helper cell-mediated antitumor immunity: T helper 2 cells in focus

“… 30 In contrast, Tregs, which are associated with poor prognosis and inhibition of antitumor immunity, can be related to better prognosis in colorectal, head and neck, esophageal, and ovarian cancers. 31 , 32 Further complicating matters, recent studies reported the presence of mixed phenotypes of Th cells (Th1/Th2) infiltrating tumors after immunotherapy, 33 , 34 and, for some cancers, an equilibrium between different infiltrating Th cells dictated the outcome. 35 Thus, the identification of the many variables that affect immune responses and tumor outcomes is of great value for improving therapies.…”

The role of inflammatory factors and T‐cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparin treatment on them

“…The detection of T‐lymphocyte subsets in the blood is an important method to observe the cellular immune level of the body, which plays an important role in the diagnosis, treatment, and prognosis of malignant tumors, 15 autoimmune diseases 16 and immune deficiency disease 17 . At present, more and more studies show that T‐lymphocyte subsets have abnormal changes in ovarian cancer 18 and different T lymphocytes have an important impact on the ovarian cancer development 19 . The decrease of CD4 + /CD8 + ratio is an important feature of immune deficiency disease 20 .…”

“… 17 At present, more and more studies show that T‐lymphocyte subsets have abnormal changes in ovarian cancer 18 and different T lymphocytes have an important impact on the ovarian cancer development. 19 The decrease of CD4 + /CD8 + ratio is an important feature of immune deficiency disease. 20 Serum human epididymis secretory protein‐4 (HE4) is one of the most sensitive tumor markers of ovarian cancer found in recent years.…”