The cytokine profile correlates with less tumor-infiltrating lymphocytes in luminal A breast cancer.

IF 3 3区医学 Q2 ONCOLOGY

Breast Cancer Research and Treatment Pub Date : 2024-10-14 DOI:10.1007/s10549-024-07492-7

Eri Ishikawa, Takahiro Watanabe, Takako Kihara, Mamiko Kuroiwa, Miki Komatsu, Sayaka Urano, Masayuki Nagahashi, Seiichi Hirota, Yasuo Miyoshi

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引用次数: 0

Abstract

Purpose: Tumor-infiltrating lymphocyte (TIL) levels are prognostic and predictive factors for breast cancer. Unlike other subtypes, most luminal A breast cancers are immune deserts; however, the underlying mechanisms are poorly understood.

Methods: Immune-related cytokines, chemokines, and growth factors were measured in the sera of 103 patients with breast cancer using a multiplex panel. The TILs were evaluated for hotspot lesions.

Results: Circulating interleukin 1 receptor antagonist (IL-1ra), IL-8, IL-12, IL-17, macrophage inflammatory protein-1β (MIP-1b), and platelet-derived growth factor B homodimer (PDGF-bb) concentrations were significantly associated with TIL levels. Cluster analysis using these six variables identified six clusters related to TIL levels. Breast cancers with high TILs (≥ 50%) were most frequent in cluster 3 (9 out of 15 cases, 60.0%), followed by cluster 1 (8 out of 34 cases, 23.5%), and the fewest in cluster 6 (1 out of 21 cases, 4.8%), whereas only one or three cases were present in clusters 2, 4, and 5 (p = 0.0064). Cluster 6, consisting mostly of luminal A (19 out of 21 cases, 90.5%), showed high levels of IL-12, IL-17, and PDGF-bb, and low levels of MIP-1b.

Conclusion: We identified a luminal A-associated immunosuppressive cytokine signature in circulation. These results suggest that a tumor microenvironment with high levels of IL-17 and PDGF-bb, and low levels of MIP-1b in luminal A breast cancers results in low induction of TILs. Our data may partially explain the low TIL levels observed in the patients with luminal A breast cancer.

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细胞因子谱与管腔 A 型乳腺癌中肿瘤浸润淋巴细胞较少有关。

目的：肿瘤浸润淋巴细胞（TIL）水平是乳腺癌的预后和预测因素。与其他亚型乳腺癌不同，大多数管腔 A 型乳腺癌是免疫荒漠；然而，对其潜在机制却知之甚少：方法：使用多重检测板测定了 103 名乳腺癌患者血清中的免疫相关细胞因子、趋化因子和生长因子。结果：循环中的白细胞介素 1 受体和白细胞介素 2 受体在乳腺癌患者血清中的比例为 1:1：结果：循环中白细胞介素 1 受体拮抗剂（IL-1ra）、IL-8、IL-12、IL-17、巨噬细胞炎症蛋白-1β（MIP-1b）和血小板衍生生长因子 B 同源二聚体（PDGF-bb）的浓度与 TIL 水平显著相关。利用这六个变量进行的聚类分析确定了六个与TIL水平相关的聚类。TIL水平高（≥50%）的乳腺癌以第3群组最多（15例中有9例，占60.0%），其次是第1群组（34例中有8例，占23.5%），第6群组最少（21例中有1例，占4.8%），而第2、4和5群组仅有1或3例（P = 0.0064）。群组 6 主要由腔隙 A 组成（21 例中有 19 例，占 90.5%），其 IL-12、IL-17 和 PDGF-bb 水平较高，而 MIP-1b 水平较低：结论：我们在血液循环中发现了与管腔 A 相关的免疫抑制细胞因子特征。这些结果表明，管腔A型乳腺癌的肿瘤微环境中IL-17和PDGF-bb水平较高，而MIP-1b水平较低，导致TILs诱导率较低。我们的数据可以部分解释管腔A型乳腺癌患者体内TIL水平较低的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast Cancer Research and Treatment 医学-肿瘤学

CiteScore

6.80

自引率

2.60%

发文量

342

审稿时长

1 months

期刊介绍： Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.