Lindberg Ida, Saleh Aya, Tutzauer Julia, Gunnarsdottir Frida Björk, Rydén Lisa, Bergenfelz Caroline, Larsson Anna-Maria
Department of Translational Medicine, Division of Experimental Infection Medicine, Lund University, 221 84, Lund, Sweden.
Department of Clinical Sciences Lund, Division of Oncology, Lund University, 221 84, Lund, Sweden.
Cancer Immunol Immunother. 2025 Jan 3;74(2):42. doi: 10.1007/s00262-024-03892-2.
Metastatic breast cancer (MBC) is generally considered an incurable disease and even though new treatments are available, the median survival is approximately three years. The introduction of immune therapies for MBC highlights the importance of the immune system in cancer progression and treatment. CD163 anti-inflammatory myeloid cells, including tumor associated macrophages (TAMs), are known to be of relevance in early breast cancer but their role in MBC is not yet established. Here we determine the levels of CD163 immune cells in 139 patients with newly diagnosed MBC by using Immunohistochemistry (IHC) and gene expression analyses (GEX). We aim to determine changes and distribution of CD163 immune cells during tumor progression from primary tumors (PT) to lymph node metastases (LNM) and distant metastases (DM). In addition, we evaluate associations between CD163 immune cells, clinicopathological factors and disease outcome (progression-free and overall survival; PFS and OS, respectively). Despite similar distribution, high levels of CD163 immune cells in the tumor nest of PT, but not in LNM or DM, associated with adverse prognostic features including higher grade and molecular subtype, as well as with shorter PFS and OS, however this observation was not significant after adjusted multivariate analyses. Finally, high levels of CD163 immune cells in PT, as well as GEX in PT and synchronous LNM associated with shorter OS from the initial diagnosis. These results indicate that evaluating the levels of CD163 immune cells may identify MBC patients with a worse prognosis. Unraveling the role of CD163 immune cells in the complex immune responses in MBC is highly relevant for improving future immune therapies.
转移性乳腺癌（MBC）通常被认为是一种无法治愈的疾病，尽管有新的治疗方法可用，但其中位生存期约为三年。MBC免疫疗法的引入凸显了免疫系统在癌症进展和治疗中的重要性。已知包括肿瘤相关巨噬细胞（TAM）在内的CD163抗炎性髓样细胞在早期乳腺癌中具有相关性，但其在MBC中的作用尚未明确。在此，我们通过免疫组织化学（IHC）和基因表达分析（GEX）确定了139例新诊断MBC患者中CD163免疫细胞的水平。我们旨在确定从原发性肿瘤（PT）到淋巴结转移（LNM）和远处转移（DM）的肿瘤进展过程中CD163免疫细胞的变化和分布。此外，我们评估了CD163免疫细胞、临床病理因素与疾病结局（无进展生存期和总生存期；分别为PFS和OS）之间的关联。尽管分布相似，但PT肿瘤巢中高水平的CD163免疫细胞（而非LNM或DM中）与不良预后特征相关，包括更高的分级和分子亚型，以及更短的PFS和OS，然而在调整后的多变量分析后，这一观察结果并不显著。最后，PT中高水平的CD163免疫细胞以及PT和同步LNM中的GEX与初始诊断后的较短OS相关。这些结果表明，评估CD163免疫细胞水平可能识别出预后较差的MBC患者。阐明CD163免疫细胞在MBC复杂免疫反应中的作用对于改善未来的免疫治疗具有高度相关性。
