Noer Julie B, Talman Maj-Lis M, Moreira José M A
Faculty of Health and Medical Sciences, Institute of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.
Diagnostic Center, Department of Pathology, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
Cancers (Basel). 2021 Dec 8;13(24):6179. doi: 10.3390/cancers13246179.
The triple-negative breast cancer (TNBC) subtype, defined as negative for ER, PgR, and HER2, is biologically more aggressive and with a poorer prognosis than the other subtypes, in part due to the lack of suitable targeted therapies. Consequently, identification of any potential novel therapeutic option, predictive and/or prognostic biomarker, or any other relevant information that may impact the clinical management of this group of patients is valuable. The HLA class II histocompatibility antigen γ chain, or cluster of differentiation 74 (CD74), has been associated with TNBCs, and poorer survival. However, discordant results have been reported for immunohistochemical studies of CD74 expression in breast cancer. Here we report validation studies for use of a novel CD74 antibody, UMAb231. We used this antibody to stain a TMA including 640 human breast cancer samples, and found no association with the TNBC subtype, but did find a positive correlation with outcome. We also found associations between CD74 expression and immune cell infiltration, and expression of programmed death ligand 1 (PD-L1). Given that CD74 may play a role in innate immune system responses and the potential of immunotherapy as a viable treatment strategy for TNBCs, CD74 expression may have predictive value for immune checkpoint therapies.
三阴性乳腺癌（TNBC）亚型定义为雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体2（HER2）均呈阴性，其生物学行为更具侵袭性，预后比其他亚型更差，部分原因是缺乏合适的靶向治疗方法。因此，确定任何潜在的新型治疗方案、预测和/或预后生物标志物，或任何可能影响该组患者临床管理的其他相关信息都具有重要价值。人类白细胞抗原II类组织相容性抗原γ链，即分化簇74（CD74），与三阴性乳腺癌相关，且与较差的生存率有关。然而，关于乳腺癌中CD74表达的免疫组织化学研究结果并不一致。在此，我们报告了一种新型CD74抗体UMAb231的验证研究。我们使用该抗体对包含640个人类乳腺癌样本的组织芯片进行染色，发现其与三阴性乳腺癌亚型无关，但与预后呈正相关。我们还发现CD74表达与免疫细胞浸润以及程序性死亡配体1（PD-L1）的表达之间存在关联。鉴于CD74可能在先天性免疫系统反应中发挥作用，且免疫疗法有可能成为三阴性乳腺癌的可行治疗策略，CD74表达可能对免疫检查点疗法具有预测价值。
