Abstract
BackgroundThe 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).MethodsA 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.ResultsIn 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 disease-free 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).ConclusionsTNBC 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.
Highlights
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)
Search results and study characteristics A total of 3194 articles were selected through searching the chosen electronic databases, and an additional 5 records were identified by cross-checking the bibliographies of retrieved meta-analysis or relevant reviews
TILs and pathological complete response (pCR) From the 11 studies demonstrating the prognostic value of TILs for pCR among TNBC patients, the results showed that upregulation of TILs predicted a higher pCR rate
Summary
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). The microenvironment of breast cancer contains a variety of cell types, including tumor-infiltrating lymphocytes (TILs). According to the results of a meta-analysis in 2014, the level of TILs was positively associated with a the prognosis of TNBC [6]. FOXP3+ T-cell infiltration was found to predict a worse prognosis via the mediation of tumor immune escape [9, 10]. Because TNBC has unique clinicopathological and immunohistochemical features, determining the clinical associations of the total TIL count or the levels of specific subtypes of TILs in TNBC can improve our ability to predict the prognostic pattern and treatment response for TNBC
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