背景:与其他种族/族裔群体相比,患有乳腺癌的非裔美国人(AA)的生存率更高。迄今未研究的结果差异是可溶性LAG-3(sLAG-3),从LAG-3免疫检查点受体切割,由于其在肿瘤微环境中的显着免疫抑制功能,LAG-3免疫检查点受体是新兴免疫疗法中失活的拟议靶标。先前的研究发现较低的sLAG-3基线水平与不良结局相关。
方法:在95例原发性乳腺癌患者的横断面研究中(n=58白种人,n=37AA),我们使用非参数Mann-Whitneyu-Test对独立样本测量了治疗前血液样本中的sLAG-3(ELISApg/ml),and,按种族计算sLAG-3与循环细胞因子的Pearsonr相关系数。
结果:与高加索患者相比,AA患者的平均sLAG-3水平较低(1377.6vs3690.3,P=.002),三阴性乳腺癌(TNBC)患者与非TNBC恶性肿瘤患者相比(P=0.02)。当TNBC肿瘤患者被排除在分析之外时,AA患者(n=21)和白种人患者(n=40)的sLAG-3水平差异显著(1937.4vs4182.4,P=.06).在白种人患者中,sLAG-3与IL-6、IL-8和IL-10相关(r=.69,P<.001;r=.70,P<.001;r=.46,P=.01;分别)。对于AA患者,sLAG-3仅与IL-6相关(r=.37,P=.03)。
结论:我们首次报道非裔美国人乳腺癌患者治疗前sLAG-3水平相对较低,独立于TNBC地位,与循环细胞因子的共表达减少。裂解LAG-3的机制和预后作用,特别是在不同的结果中,还有待阐明。
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.