Bobrie Angélique, Massol Océane, Ramos Jeanne, Mollevi Caroline, Lopez-Crapez Evelyne, Bonnefoy Nathalie, Boissière-Michot Florence, Jacot William
Department of Medical Oncology, Institut Régional du Cancer de Montpellier (ICM), 34298 Montpellier, France.
Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Institut du Cancer Montpellier (ICM), 34298 Montpellier, France.
Cancers (Basel). 2022 Oct 3;14(19):4829. doi: 10.3390/cancers14194829.
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.
三阴性乳腺癌（TNBC）预后较差，但可能对免疫疗法有反应。巨噬细胞是可塑性细胞，可呈现多种表型和功能。虽然它们是TNBC中的主要免疫细胞群体，但肿瘤相关巨噬细胞（TAM）与TNBC进展之间的关系鲜有研究，结果也存在争议。方法：我们在一个有详尽描述的285例非转移性TNBC患者队列中，通过使用抗CD68、-IRF8、-CD163和-CD206抗体进行免疫组织化学定量评估TAM的预后影响。结果：CD68（p = 0.008）、IRF8（p = 0.001）和CD163（p < 0.001）表达与更高的肿瘤分级呈正相关，而CD206与更小的肿瘤大小相关（p < 0.001）。所有巨噬细胞标志物均与更高的肿瘤浸润淋巴细胞数量和PD-L1表达相关。单因素生存分析显示，CD163 +或CD206 + TAM与无复发生存之间存在显著正相关（分别为：HR = 0.52 [0.28 - 0.97]，p = 0.027，以及HR = 0.51 [0.31 - 0.82]，p = 0.005），以及CD206 + TAM与总生存之间存在显著正相关（HR = 0.54 [0.35 - 0.83]，p = 0.005）。在多因素分析中，CD206 + TAM与无复发生存之间存在关联趋势（HR = 0.63 [0.33 - 1.04]，p = 0.073）。结论：这些数据表明，CD206表达定义了一个可能与TNBC患者良好预后相关的TAM亚群。CD206表达可能识别出一个具有特定治疗选择的免疫TNBC亚组。
