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. 2021 Mar 16;21(1):286.
doi: 10.1186/s12885-021-08009-x.

Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast

Hajime Kuroda  1   2 , Tsengelmaa Jamiyan  3   4 , Rin Yamaguchi  5 , Akinari Kakumoto  6   7 , Akihito Abe  8 , Oi Harada  9 , Atsuko Masunaga  6
Affiliations

Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast

Hajime Kuroda et al. BMC Cancer. .

Abstract

Background: In 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.

Methods: We 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.

Results: The 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.

Conclusions: CD20+ 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.

Keywords: Breast; Triple-negative cancer; Tumor-infiltrating B lymphocytes; Tumor-infiltrating T lymphocytes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Representative photomicrographs of TILs in patients with TNBC. A patient with a high level of TILs on HE staining (a). IHC using primary antibodies against CD4 (b), CD8 (c), CD20 (d), CD25 (e), and FOXP3 (f) to characterize TILs in the same section of tumor tissue (original magnification, × 400)
Fig. 2
Fig. 2
Absolute counts of CD20+ TILs and CD4+, CD8+, CD25, and FOXP3+ TILs in the peripheral stroma of patients with TNBC. The horizontal and vertical reference lines display absolute numbers of CD20+ TILs and CD4+, CD8+, CD25+, and FOXP3+ TILs. As shown by the regression lines, counts of CD4+, CD8+, and FOXP3+ TILs increased along with CD20+ TILs in TNBC. However, the counts of CD25+ were not related to CD20+ TILs
Fig. 3
Fig. 3
Box plots displaying the correlation of CD20+ TILs with the absolute numbers of CD4+, CD8+, FOXP3+, and CD25 TILs in patients with TNBC. The bars are median values, the box displays the interquartile range (25–75%), and the whiskers extend to 1.5 x the interquartile range
Fig. 4
Fig. 4
Kaplan-Meier plots showing RFS and OS in TNBC according to infiltration of CD20+ TILs. Log-rank tests were used to estimate P-values
Fig. 5
Fig. 5
Densities of TIL-B and TIL-T are associated with patient survival. Kaplan-Meier curves showing RFS and OS of the patients by combining CD20+ with CD4+, CD8+, CD25+, and FOXP3+ TILs. a, b CD20-high CD4-high (n = 30), CD20-high CD4-low (n = 23), CD20-low CD4-high (n = 22), CD20-low CD4-low (n = 32). c, d CD8-high CD4-high (n = 31), CD20-high CD8-low (n = 22), CD20-low CD8-high (n = 22), CD20-low CD8-low (n = 32). e, f CD20-high CD25-high (n = 27), CD20-high CD25-low (n = 26), CD20-low CD25-high (n = 26), CD20-low CD25-low (n = 28). g, h CD20-high FOXP3-high (n = 28), CD20-high FOXP3-low (n = 25), CD20-low FOXP3-high (n = 23), CD20-low FOXP3-low (n = 31). Graph shows p = log-rank test P-values
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