Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis

Abstract

Background: The objective of this systematic review and meta-analysis was to determine the prognostic value of total tumor-infiltrating lymphocytes (TILs) and subtypes of TILs (CD4 + , CD8 + , and FOXP3 + ) in triple-negative breast cancer (TNBC). Methods:A systematic search of the MEDLINE, EMBASE, and Web of Science databases was conducted to identified eligible articles published before August 2019. Study screening, data extraction, and risk of bias assessment were performed by two independent reviewers. Risk of bias on the study level was assessed using the ROBINS I tool and Quality in Prognosis Studies (QUIPS) tool. We performed a meta-analysis to obtain a pooled estimate of the prognostic role of TILs using Review Manager 5.3. Results:In total, 37 studies were included in the final analysis. Compared to TNBC patients with low TIL levels, TNBC patients with high TIL levels showed a higher rate of pathological complete response (pCR) to treatment (odds ratio [OR] 2.14, 95% confidence interval [CI] 1. 43-3.19). With each 10% increase in percentage of TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with low TIL levels, patients with high TIL levels had better overall survival (OS; hazard ratio [HR] 0.58, 95% CI 0.48-0.71) and diseasefree survival (DFS; HR 0.66, 95% CI 0.57-0.76). Additionally, with a continuous increase in TIL levels, patients with TNBC had improved OS (HR 0.90, 95% CI 0.87-0.93) and DFS (HR 0.92, 95% CI 0.90-0.95). A high CD4 + TIL level was associated with better OS (HR 0.49, 95% CI 0.32-0.76) and DFS (HR 0.54, 95% CI 0.36-0.80). A high CD8 + TIL level was associated better DFS only (HR 0.55, 95% CI 0.38-0.81), as no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). A high FOXP3 + TIL level also was associated with only DFS (HR 0.50, 95% CI 0.33-0.75) and not OS (HR 1.28, 95% CI 0.24-6.88). Conclusions: TNBC with a high level of TILs showed better short-term and long-term prognoses. High levels of specific phenotypes of TILs (CD4 + , CD8 + , and FOXP3 + ) were predictive of a positive long-term prognosis for TNBC.

Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

“…Moreover, Gao et al has reported that increased TILs conferred an improved survival rate. In patients with TNBC, CD4 + , CD8 + , and FOXP3 + lymphocytes have been indicative of a favorable prognosis [30].…”

Comparison of Nottingham Prognostic Index, PREDICT and PrognosTILs in Triple Negative Breast Cancer –a Retrospective Cohort Study

“…1 Kaplan-Meier analysis of NPI. According to the log rank test significant differences were observed between the overall survival (OS) estimates of MPG1 vs. PPG (p = 0.017), MPG1 vs. VPPG (p = 0.049) andMPG2 vs. PPG (p = 0.026); and the disease-free survival (DFS) estimates of PPG vs. MPG1 (p = 0.002), PPG vs. MPG2 (p = 0.035), PPG vs. prognosticator of TNBCs [24], and the prognostic value of TILs was also found in a more recent meta-analysis [34]. When prognostic factors show divergent features, i.e.…”

Adoptive Cell Therapy in Breast Cancer: A Current Perspective of Next-Generation Medicine

“…BC, particularly HER2 + and luminal-like tumors, have been traditionally considered as poorly immunogenic, with low numbers of TILs and a limited burden of neoantigens (3,14,15). However, a robust correlation exists between increased stromal TILs and a better prognosis in TNBC (16)(17)(18)(19).…”