Abstract

BackgroundIn this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method.MethodsWe investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available.ResultsThe strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis.ConclusionsCD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.

Highlights

  • In this study, we investigated CD20+ Tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and Forkhead box protein 3 (FOXP3)+), including their combined prognostic value using an immunohistochemical staining method

  • We previously found that CD4+ and CD8+ TILs are correlated with a favorable prognosis in triple-negative breast cancer (TNBC) [11]

  • TILs that contain both TIL-B and TIL-T are correlated with lymphocyte proliferation and a good prognosis, suggesting that TIL-B cooperate with TIL-T in an anti-tumor reaction [25]

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Summary

Introduction

We investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. The prognostic correlation of TILs-T has been widely reported, there are few studies on Kuroda et al BMC Cancer (2021) 21:286 infiltrating B lymphocytes (TILs-B) in breast cancer and there is no consensus on their prognostic impact [12,13,14,15,16,17,18,19,20]. High infiltration of Treg lymphocytes was reported to be correlated with a negative prognosis in human cancers, including breast cancer, and they may represent a new therapeutic target [26,27,28,29,30,31]. TIL-B and Treg lymphocyte involvement in human cancer remains unclear

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