Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis

Abstract

Background: Tumor-infiltrating lymphocytes (TILs) are involved in the antitumor immune response. The association between prognosis in patients with TILs and high-grade serous ovarian cancer (HGSOC) remains obscure, with some studies reporting conflicting results. Methods: We conducted an extensive literature search of electronic databases and retrieved prognostic data of each selected subtype of TILs, including CD3+, CD4+, CD8+, CD103+, and PD-1+ TILs. The fixed-effects model was applied to derive the pooled hazard ratio (HR) and 95% confidence interval (CI) of these markers. Results: The systematic review process yielded 19 eligible studies comprising 6004 patients with HGSOC. We compared TIL-positive and TIL-negative patients, and the pooled HRs from the multivariate analysis revealed that intraepithelial CD8+ TILs were positively correlated with progression-free survival (PFS, HR 0.46, 95% CI 0.25–0.67) and overall survival (OS, HR 0.90, 95% CI 0.86–0.9); stromal CD8+ TILs were positively correlated with OS (HR 0.61, 95% CI 0.36–0.87). Furthermore, the pooled HRs from univariate analysis demonstrated that intraepithelial CD3+, CD4+, CD8+, and CD103+ TILs were positively associated with OS (HR 0.58, 95% CI 0.44–0.72; HR 0.37, 95% CI 0.16–0.59; HR 0.51, 95% CI 0.42–0.60, and HR 0.59, 95% CI 0.44–0.74, respectively); stromal CD4+ and CD8+ TILs were significantly associated with OS (HR 0.63, 95% CI 0.32–0.94 and HR 0.78, 95% CI 0.58–0.97, respectively). However, the pooled HR from the multivariate analysis revealed that PD-1+ TILs were not associated with the OS of patients with HGSOC (HR 0.97, 95% CI 0.90–1.04). Conclusion: This meta-analysis provided evidence of the association of CD3+, CD4+, CD8+, and CD103+ TILs with the survival benefits (OS and PFS) of patients with HGSOC.

Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis

“…This low number of T-cells is in keeping with findings of multiple investigators that PCa is an immunologically “cold” tumor with low numbers of tumor infiltrating lymphocytes (TILs) [19] . Although various definitions and quantification methods have been used for TILs, CD3 + total T-cells and subsets, especially CD8 + T-cells are shown in other cancers to correlate with survival [20] , [21] .

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Evolution of Immunotherapy for Ovarian Cancer from a Bird’s-Eye Perspective: A Text-Mining Analysis of Publication Trends and Topics

“…For example, adipose tissues can secrete many types of cytokines and molecular factors to recruit macrophages to attenuate T cell function ( 52 , 53 ). Several research studies have investigated the correlation between TIL and prognosis of OC and identified several T cell predictive biomarkers, such as CD4, CD8, CD3, CD103, and PD-1 ( 54 ).…”

Effect of MAP3K8 on Prognosis and Tumor-Related Inflammation in Renal Clear Cell Carcinoma

“…According to previous studies and the results in this study, effects of MAP3K8 on cancer-related inflammation in ccRCC may be double-edged. On one hand, ccRCC patients with highlevel expression of MAP3K8 negatively correlated with the presence of T cell CD4 + Th1, non-regulatory T cell CD4 + , and NK cell, suggesting a potential protumorigenic role of MAP3K8 because CD4 + TILs and NK cells were reported to associate with better OS in cancers (Hao et al, 2020). In addition, CD4 + Th1 secreting cytokines such as TNF may effectively inhibit angiogenesis as well as facilitate the activation and proliferation of CD8 + TILs, which could directly kill tumor cells (Ovarian Tumor Tissue Analysis [OTTA] Consortium, Goode et al, 2017;Hao et al, 2020).…”