Abstract
PurposeImmune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated.MethodsWe evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. ResultsTNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. ConclusionsOur study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.
Highlights
Cancers historically described as medullary carcinoma, or carcinoma with medullary features, were previously recognized as a specific, special type of well-circumscribed breast cancer with a prominent tumor-infiltrating lymphocyte (TIL) and macrophage infiltrate, and associated with better prognosis than other stage-matched high-grade cancers
Our study suggests that tumor-associated macrophages (TAMs) further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs
The process of TME is highly complex in Triple-negative breast cancer (TNBC) and for an improved understanding, larger validation studies are necessary to confirm these findings
Summary
Cancers historically described as medullary carcinoma, or carcinoma with medullary features, were previously recognized as a specific, special type of well-circumscribed breast cancer with a prominent tumor-infiltrating lymphocyte (TIL) and macrophage infiltrate, and associated with better prognosis than other stage-matched high-grade cancers. “carcinoma with medullary features” has suffered from poor interobserver reproducibility and overlapping features with Triple-negative breast cancer (TNBC). TNBC is characterized by a lack of expression of the estrogen receptor (ER) and progesterone receptor (PgR), and absence of human epidermal growth factor receptor 2 (HER2) protein overexpression; this type is known to have a poor prognosis and to recruit TILs and tumor-associated macrophages (TAMs). The latest WHO classification proposed considering carcinomas with a medullary pattern as representing one end of the spectrum of TILrich invasive breast carcinoma of no special type (IBC-NSTs), rather than a distinct morphological subtype, and to use the term “IBC-NST with medullary pattern” [4]
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