B7同源物4（B7-H4）和吲哚胺2,3-双加氧酶（IDO1）是抗肿瘤活性抑制的因子，也是免疫检查点治疗的新治疗靶点。我们的研究旨在同时研究三阴性乳腺癌（TNBC）中B7-H4、IDO1和程序性细胞死亡配体1（PD-L1）表达之间的相互关系，包括肿瘤免疫微环境（TIME）和TNBC亚型。对119例TNBC的全切片进行了PD-L1、B7-H4和IDO1的免疫组织化学染色。根据间质肿瘤浸润淋巴细胞（sTILs）的百分比、TILs的模式分类、肿瘤间质比（TSR）和三级淋巴结构（TLS）对TIME进行了评估。TNBC亚型也通过细胞角蛋白5/6和雄激素受体（AR）的免疫组织化学分析确定。 结果显示，B7-H4表达在PD-L1（28-8克隆）的联合阳性得分阈值为5的病例中明显增高（p = 0.021），在炎症型TIL模式（p = 0.007）和TLS ≥4（p = 0.006）的病例中也较高。在角蛋白5/6 ≥10的病例中，B7-H4表达较高（p = 0.035）。AR和B7-H4的H评分呈负相关（ρ = -0.509，p <0.001）。在AR <10的病例中，B7-H4和IDO1的表达水平呈负相关（ρ = -0.354，p <0.001）。 这些结果表明，考虑TIL模式和TLS，并确定PD-L1和基底样型的表达对于估计B7-H4的表达是有用的。此外，在雄激素受体（LAR）型中，B7-H4的表达缺乏。在非LAR亚型中，B7-H4和IDO1的表达是互斥的。 ©2023. 作者（们）, 在The Japanese Breast Cancer Society的独家许可下。

B7 homolog 4 (B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes.Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor-stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression.B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8; p = 0.021), inflamed TIL pattern (p = 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = - 0.509, p < 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (ρ = - 0.354, p < 0.001).These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.