Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;23(12):2513-2525.
doi: 10.1007/s12094-021-02652-3. Epub 2021 Jun 5.

Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

H Kuroda  1   2 , T Jamiyan  3   4 , R Yamaguchi  5 , A Kakumoto  6   7 , A Abe  8 , O Harada  9 , A Masunaga  6
Affiliations

Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

H Kuroda et al. Clin Transl Oncol. 2021 Dec.

Abstract

Purpose: Immune 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.

Methods: We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC.

Results: TNBCs 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.

Conclusions: Our 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.

Keywords: Triple-negative breast cancer; Tumor microenvironment; Tumor-associated macrophages; Tumor-infiltrated immune cells; Tumor-infiltrating lymphocytes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no potential competing interests.

Figures

Fig. 1
Fig. 1
Representative hematoxylin and eosin and immunohistochemistry images showing tumor microenvironments with lower and higher densities. At 400× magnification
Fig. 2
Fig. 2
Kaplan–Meier curves showing the relapse-free survival and overall survival of patients with certain densities of CD68+ TAMs versus densities of TILs. a, b CD68+ TAMs/CD4+ TILs. c, d CD68+ TAMs/CD8+ TILs. e, f CD68+ TAMs/CD20+ TILs. TILs tumor-infiltrating lymphocytes, TAMs tumor-associated macrophages
Fig. 3
Fig. 3
Kaplan–Meier curves showing the relapse-free survival and overall survival of patients with certain densities of CD163+ TAMs versus densities of TILs. a, b CD163+ TAMs/CD4+ TILs. c, d CD163+ TAMs/CD8+ TILs. e, f CD163+ TAMs/CD20+ TILs. TILs tumor-infiltrating lymphocytes, TAMs tumor-associated macrophages
Fig. 4
Fig. 4
Schema of the interaction of immune cells in the breast cancer tumor microenvironment. CD4+ /CD8+ /CD20+ TILs directly kill the tumor cells. TILs are supported by TAM1s and suppress the tumor cells. In contrast, TAM2s exerts an immunosuppressive function via the inhibition of T cells and B cells, indicating tumorigenic roles. TILs tumor-infiltrating lymphocytes, TAM1s tumor-associated macrophages-1, TAM2s tumor-associated macrophages-2
See this image and copyright information in PMC

References

    1. Park JH, Jonas SF, Bataillon G, Criscitiello C, Salgado R, Loi S, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. 2019;30:1941–1949. doi: 10.1093/annonc/mdz395. - DOI - PubMed
    1. Matkowski R, Gisterek I, Halon A, Lacko A, Szewczyk K, Staszek U, et al. The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer. Anticancer Res. 2009;29:2445–2451. - PubMed
    1. Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014;25:1536–1543. doi: 10.1093/annonc/mdu191. - DOI - PubMed
    1. Lokuhetty D, White V, Watanabe R, Cree I. WHO classification of breast tumours. 5. Lyon: IARC; 2019.
    1. Jamiyan T, Kuroda H, Yamaguchi R, Nakazato Y, Noda S, Onozaki M, et al. Prognostic impact of a tumor-infiltrating lymphocyte subtype in triple negative cancer of the breast. Breast Cancer. 2020;27:880–892. doi: 10.1007/s12282-020-01084-1. - DOI - PMC - PubMed

Substances