Association of CD206 Protein Expression with Immune Infiltration and Prognosis in Patients with Triple-Negative Breast Cancer

Simple Summary Triple-negative breast cancers (TBNCs) represent 10-20% of all breast cancers. TNBCs are more frequent in younger women, and present more aggressive features and poorer prognosis. Few specific therapeutics are available for TNBC treatment and it is crucial to better characterize TNBC biology in order to discover new therapeutic targets. In this study, we focused on the immune tumor microenvironment, particularly on macrophages that have been less studied in the context of TNBC. Macrophages are very plastic cells; their phenotype and function can change depending upon environmental conditions. Therefore, we used four macrophage markers to quantify the macrophage infiltrate (CD68, IRF8, CD163, and CD206) in tumors from 285 patients with TNBC. We demonstrated for the first time that a population of macrophages, defined by CD206 expression, delineates a subgroup of TNBCs that may have a better prognosis. These results could help to refine the patients' prognosis and develop new therapeutic strategies. Background: Triple-negative breast cancers (TNBCs) have a worse prognosis, but might respond to immunotherapies. Macrophages are plastic cells that can adopt various phenotypes and functions. Although they are a major immune population in TNBCs, the relationship between tumor-associated macrophages (TAMs) and TNBC progression has been rarely explored, with controversial results. Methods: We evaluated the prognostic impact of TAMs, quantified by immunohistochemistry with anti-CD68, -IRF8, -CD163, and -CD206 antibodies, in a well-described cohort of 285 patients with non-metastatic TNBC. Results: CD68 (p = 0.008), IRF8 (p = 0.001), and CD163 (p < 0.001) expression positively correlated with higher tumor grade, while CD206 was associated with smaller tumor size (p < 0.001). All macrophage markers were associated with higher tumor-infiltrating lymphocyte numbers and PD-L1 expression. Univariate survival analyses reported a significant positive correlation between CD163(+) or CD206(+) TAMs and relapse-free survival (respectively: HR = 0.52 [0.28-0.97], p = 0.027, and HR = 0.51 [0.31-0.82], p = 0.005), and between CD206(+) TAMs and overall survival (HR = 0.54 [0.35-0.83], p = 0.005). In multivariate analysis, there was a trend for an association between CD206(+) TAMs and relapse-free survival (HR = 0.63 [0.33-1.04], p = 0.073). Conclusions: These data suggest that CD206 expression defines a TAM subpopulation potentially associated with favorable outcomes in patients with TNBC. CD206 expression might identify an immune TNBC subgroup with specific therapeutic options.

Automated summary

This study focused on the immune tumor microenvironment in triple-negative breast cancer (TNBC), specifically investigating the role of macrophages. The findings revealed that a subgroup of TNBCs characterized by CD206 expression in macrophages may have a better prognosis, suggesting potential therapeutic options for this immune TNBC subgroup.