文章：

肿瘤相关中性粒细胞在缺乏免疫抑制性巨噬细胞募集的早期管腔型乳腺癌中为不良预后因素

Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment

原文发布日期：15 September 2024

DOI: 10.3390/cancers16183160

类型: Article

开放获取: 是

英文摘要：

Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs.

摘要翻译： 

背景：肿瘤相关中性粒细胞（TANs）是肿瘤微环境的重要调节因子，具有促进和抑制肿瘤进展的双重功能。TANs在早期管腔型乳腺癌中的预后作用尚不明确。方法：作为加速部分乳腺照射（APBI）II期试验的一部分，共有144名早期激素受体阳性乳腺癌患者接受治疗。将来自多个部位的切除样本制成组织芯片，并通过免疫组化染色检测CD66b+中性粒细胞。分别在间质和上皮内区域测量CD66b+中性粒细胞密度。结果：在中央肿瘤样本中，高间质和上皮内CD66b+ TAN密度是负面预后因素。此外，邻近正常乳腺组织和淋巴结样本中的中性粒细胞密度也与无病生存期降低相关。TAN密度与CD163+ M2样肿瘤相关巨噬细胞（TAM）密度相关，我们在先前研究中已分析过后者。在M1/M2 TAM比率升高的肿瘤中，TANs是负面预后因素，而在M1/M2比率较低的肿瘤中，这种对患者结局的影响消失。对TAM和TAN密度的联合多变量分析显示，仅TAM极化状态是独立的预后因素。结论：在单标记物分析中，CD66b+中性粒细胞是早期管腔型乳腺癌的负面预后因素。未来研究中可能需要结合TAMs进行联合分析，以正确评估其预后影响。TAN的募集可能作为一种免疫逃逸和疾病进展的补偿机制，作用于那些无法充分吸引和极化TAMs的肿瘤。

原文链接：

Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment