CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women's Circle of Health Study and the Women's Circle of Health Follow-Up Study

Breast Cancer Res. 2024 May 8;26(1):75. doi: 10.1186/s13058-024-01831-8.

Abstract

Background: Tumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes.

Methods: We investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women's Circle of Health Study and Women's Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43-12.33).

Results: Women with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16-0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12-0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71-1.10).

Conclusions: In contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer. Trial registration Not applicable.

Keywords: Breast cancer; CD163; Prognosis; Survival; Tumor-associated macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD* / metabolism
  • Antigens, Differentiation, Myelomonocytic* / metabolism
  • Biomarkers, Tumor / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Cell Surface* / metabolism
  • Triple Negative Breast Neoplasms* / immunology
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / mortality
  • Triple Negative Breast Neoplasms* / pathology
  • Tumor Microenvironment* / immunology
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • CD163 antigen
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, CD
  • Receptors, Cell Surface
  • Biomarkers, Tumor