Objective
The objective of this systematic review and meta-analysis is to determine prognostic roles of the total tumor-infiltrating lymphocytes (TILs) or subtypes of TILs (CD4+, CD8+, and FOSP3+) for patients with triple-negative breast cancer (TNBC).
Methods
A systematic literature search was conducted in the databases of MEDLINE, EMBASE, and Web of Science to identified eligible articles before August 2019. Study screening, data extraction, and risk of bias were performed by two independent reviewers. Risk of bias on study level was assessed using an approach based on the ROBINS I tool and the Quality In Prognosis Studies (QUIPS) tool. We performed meta-analyses to obtain a pooled estimate of the prognostic role of TILS using Review Manager 5.3.
Results
There was total of 37 studies included in the final analysis. Compared to TNBC patients with poor TILs, TNBC patients with rich TILs had a higher pCR to treatments (OR 2.14, 95% CI 1.43-3.19). Along with per 10% increase of the TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with poor TILs, patients with rich TILs had a better OS (HR 0.58, 95% CI 0.48-0.71) and DFS (HR 0.66, 95% CI 0.57-0.76). Addition to, along with a continuous increase of the TILs, 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) as well. CD4+TILs subgroup (rich vs. poor) showed a better OS (HR 0.49, 95%CI 0.32-0.76) and DFS (HR 0.54, 95%CI 0.36-0.80). CD8+TILs subgroup (rich vs. poor) showed a better DFS (HR 0.55, 95% CI 0.38-0.81), but no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). FOXP3+TILs subgroup (rich vs. poor) showed a better DFS (HR 0.50, 95% CI 0.33-0.75), but no statistical association was found with OS (HR 1.28, 95% CI 0.24-6.88).
Conclusion
TNBC with higher levels of TILs showed better short-term and long-term prognosis. The phenotypes of TILs (CD4+TILs, CD8+TILs, and FOXP3+TILs) had positive prediction for long-term prognosis for TNBC.