The prognostic value of tumor-infiltrating T lymphocytes in ovarian cancer

Abstract

The prognostic value of tumor-infiltrating lymphocytes (TILs) in ovarian cancer is still in controversial. This study is aimed to assess the impact of different TIL subsets on the progression free survival (PFS)/disease free survival (DSS) and overall survival (OS)/disease specific survival (DSS) in ovarian cancer. A comprehensive literature search in PubMed, ISI Web of Science, and Medline was performed to identify relevant studies evaluating the prognostic value of TILs in ovarian cancer. Reviews of each study were conducted and data were extracted. The main outcomes analyzed were PFS/DFS and OS/DSS. A total of 21 eligible studies enrolling 2903 ovarian cancer patients were included for the meta-analysis. The overall analysis revealed that intraepithelial CD3+ and CD8+ TILs were strongly associated with improved PFS/DFS (HR=0.53, for CD3+ TILs; and HR=0.50, for CD8+ TILs). Intraepithelial CD8+/Foxp3+ ratios appeared to be associated with improved PFS, though without reaching statistical significance (HR=0.73). Moreover, intraepithelial CD3+, CD8+, and CD103+ TILs were clearly associated with increased OS/DSS (HR=0.50, for CD3+ TILs; HR=0.62, for CD8+ TILs; HR=0.54, for CD103+ TILs). However, intraepithelial FoxP3+ TILs, CD8+/FoxP3+ ratios, CD8+/CD4+ ratios, and stromal TILs had no impact on the OS/DSS (HR=0.98, for FoxP3+ TILs; HR=0.69, for CD8+/FoxP3+ ratios; HR=0.48, for CD8+/CD4+ ratios; HR=0.82, for stromal TILs). In conclusion, the present meta-analysis supports the hypothesis that intraepithelial TILs are predictive biomarkers for the prognosis of ovarian cancer patients. Future randomized studies are needed to verify these observations.

PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome

“…Inflammatory phenotypes of tumours displayed by presence of TIL infiltration have been linked to improved survival in various types of cancer, including HNSCC. 9,[22][23][24][25] There is evidence that the presence of PD-1-expressing TILs is independent of the amount of T cells and not only a secondary effect of an active immune response in ovarian cancer. 26 Therefore, the analysis as an independent prognostic marker is reasonable.…”

“…PD-1 expression in lymphocytes was evaluated intratumourally, based on the number of positive TILs counted in three high-power fields (HPF) (400-fold magnification) of highest density. Stratification was made for negative expression (0-5), weak (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), moderate (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) or strong (>30) infiltration patterns.…”

Integrin αvβ8 serves as a Novel Marker of Poor Prognosis in Colon Carcinoma and Regulates Cell Invasiveness through the Activation of TGF-β1

“…Integrin αvβ8 detected on tumor cells serves as a platform for TGF-β1 activation on tumor-infiltrating immune cells, which has been suggested to be a dominant mechanism of tumor immunosuppression [22]. Tumor-infiltrating CD8 + T lymphocytes, which are a crucial component of the cellular immune system, constitutes the effector arm of adaptive antitumor immunity [29,30]. We determined the association between integrin αvβ8 expression and CD8 + TILs in colon cancer by immunohistochemistry.…”

SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in ovarian cancer

“…Since several studies have reported on the role of TILs in the prognosis of ovarian cancer (Goode et al, 2017;Hwang et al, 2012;Li et al, 2017;Sato et al, 2005), and SLFN11 has been shown to be expressed in primary human Tlymphocytes (Puck et al, 2015), we evaluated TIL infiltration by CD3 and CD8 staining (analysis performed by FG), both in terms of total number/mm (total CD3+ and CD8+ TILs) and as a measure of TILs in direct contact with cancer cells, without stroma interposition (intratumoral CD3+ and CD8+ TILs) in HGSOC (Stanske et al, 2018). Using HALO, we then calculated SLFN11 overall H-scores in the studied cohort, as well as H-scores in cancer and non-cancer cells separately (see Supplementary Table 1).…”