Department of Pathology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
Department of Pathology, Kawasaki Medical School General Medical Center, Okayama, Japan.
Breast Cancer. 2023 Nov;30(6):1041-1053. doi: 10.1007/s12282-023-01498-7. Epub 2023 Aug 29.
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.
B7 同源物 4（B7-H4）和吲哚胺 2,3-双加氧酶（IDO1）是抑制抗肿瘤活性的相关因子，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 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（sTIL；%）、TIL 模式分类、肿瘤-基质比（TSR）和三级淋巴结构（TLS）评估 TIME。还通过细胞角蛋白 5/6 和雄激素受体（AR）表达的免疫组织化学分析来确定 TNBC 亚型。
B7-H4 表达在 PD-L1（克隆 28-8；p=0.021）、炎症性 TIL 模式（p=0.007）和 TLS≥4（p=0.006）的联合阳性评分截定点为 5 的病例中显著更高。在 CK5/6≥10 的病例中 B7-H4 表达更高（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，有助于估计 B7-H4 的表达。此外，Luminal 雄激素受体（LAR）型通常缺乏 B7-H4 的表达。在非 LAR 类型中，B7-H4 和 IDO1 的表达是排他的。
