高加索人和非洲裔美国人乳腺癌患者的基线 sLAG-3 水平。

IF 3 3区 医学 Q2 ONCOLOGY Breast Cancer Research and Treatment Pub Date : 2024-11-01 Epub Date: 2024-09-04 DOI:10.1007/s10549-024-07455-y
Helen Swede, Sharif M Ridwan, Jillian Strandberg, Andrew L Salner, Jonathan R Sporn, Lynn Kuo, Karen Ru, Henry M Smilowitz
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引用次数: 0

摘要

背景:与其他种族/族裔群体相比,非裔美国人(AA)乳腺癌患者的生存率一直较低,尽管最近所有种族/族裔群体的生存率都有所提高。可溶性 LAG-3(sLAG-3)是由 LAG-3 免疫检查点受体裂解而成,由于其在肿瘤微环境中具有显著的免疫抑制功能,因此被认为是新兴免疫疗法中的失活靶点。之前的一项研究发现,较低的sLAG-3基线水平与较差的预后有关:在一项针对 95 名原发性乳腺癌患者(n = 58 名白种人,n = 37 名 AA 人)的横断面研究中,我们使用非参数 Mann-Whitney u 检验法测量了治疗前血液样本中的 sLAG-3(ELISA pg/ml),并按种族计算了 sLAG-3 与循环细胞因子的 Pearson r 相关系数:结果:与白种人相比,AA 患者的平均 sLAG-3 水平较低(1377.6 vs 3690.3,P = .002);与非 TNBC 恶性肿瘤患者相比,三阴性乳腺癌(TNBC)患者的平均 sLAG-3 水平较低(P = .02)。如果将 TNBC 肿瘤患者排除在分析之外,AA 患者(21 人)和白种人患者(40 人)之间的 sLAG-3 水平差异仍然很大(1937.4 vs 4182.4,P = .06)。在白种人患者中,sLAG-3 与 IL-6、IL-8 和 IL-10 存在相关性(r = .69,P 结论:sLAG-3 与 IL-6、IL-8 和 IL-10 存在相关性:我们首次报告了非裔美国人乳腺癌患者治疗前的 sLAG-3 水平可能相对较低,与 TNBC 状态无关,同时与循环细胞因子的共表达也较低。裂解 LAG-3 的机理和预后作用,尤其是在不同结果中的作用,仍有待阐明。
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Baseline sLAG-3 levels in Caucasian and African-American breast cancer patients.

Background: Worse survival persists for African-Americans (AA) with breast cancer compared to other race/ethnic groups despite recent improvements for all. Unstudied in outcomes disparities to date is soluble LAG-3 (sLAG-3), cleaved from the LAG-3 immune checkpoint receptor which is a proposed target for deactivation in emerging immunotherapies due to its prominent immunosuppressive function in the tumoral microenvironment. A prior study has found that lower sLAG-3 baseline level was associated with poor outcomes.

Methods: In a cross-sectional study of 95 patients with primary breast cancer (n = 58 Caucasian, n = 37 AA), we measured sLAG-3 (ELISA pg/ml) in pre-treatment blood samples using the non-parametric Mann-Whitney u-Test for independent samples, and, calculated Pearson r correlation coefficients of sLAG-3 with circulating cytokines by race.

Results: Mean sLAG-3 level was lower in AA compared to Caucasian patients (1377.6 vs 3690.3, P = .002), and in patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC malignancies (P = .02). When patients with TNBC tumors were excluded from analyses, the difference in sLAG-3 level between AA (n = 21) and Caucasian patients (n = 40) substantially remained (1937.4 vs 4182.4, P = .06). Among Caucasian patients, sLAG-3 was correlated with IL-6, IL-8 and IL-10 (r = .69, P < .001; r = .70, P < .001; and, r = .46, P = .01; respectively). For AA patients, sLAG-3 was correlated only with IL-6 (r = .37, P = .03).

Conclusions: We present the first report that African-American breast cancer patients might have comparatively low pre-treatment sLAG-3 levels, independent of TNBC status, along with reduced co-expression with circulating cytokines. The mechanistic and prognostic role of cleaved LAG-3, particularly in disparate outcomes, remains to be elucidated.

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来源期刊
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.
期刊最新文献
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