基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于三阴性乳腺癌亚型的 B7-H4、IDO1 和 PD-L1 表达及肿瘤免疫微环境的免疫组织学分析
英文原题：Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes.
查看英文原题
Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes.
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研究概要
这些结果提示，考虑 TIL 模式与 TLS 并识别 PD-L1 的表达及基底样型，有助于估计 B7-H4 的表达。
中文摘要
背景
B7 同源蛋白 4（B7-H4）和吲哚胺 2,3-双加氧酶（IDO1）参与抑制抗肿瘤活性，也是免疫检查点治疗的新靶点。本研究旨在同时考察三阴性乳腺癌（TNBC）中 B7-H4、IDO1 和程序性死亡配体 1（PD-L1）的相互关系，并分析肿瘤免疫微环境（TIME）及 TNBC 亚型。
方法
对 119 例 TNBC 的全切片进行 PD-L1、B7-H4 和 IDO1 免疫染色。TIME 评估指标包括间质TIL（肿瘤浸润淋巴细胞）（sTIL，%）、TIL 模式分类、肿瘤-间质比（TSR）及三级淋巴结构（TLS）。同时通过免疫组化分析细胞角蛋白 5/6 和雄激素受体（AR）表达，以确定 TNBC 亚型。
结果
PD-L1（28-8 克隆）综合阳性评分截断值为 5 的病例（p = 0.021）、TIL 炎性模式病例（p = 0.007）及 TLS 4 级病例（p = 0.006）中，B7-H4 表达显著较高。CK5/6 ≥10 的病例 B7-H4 表达较高（p = 0.035）。AR 与 B7-H4 的 H-score 呈负相关（相关系数 = −0.509，p < 0.001）。在 AR <10 的病例中，B7-H4 与 IDO1 表达水平呈负相关（相关系数 = −0.354，p < 0.001）。
结论
结果提示，结合 TIL 模式和 TLS，并检测 PD-L1 表达及基底样亚型，有助于估计 B7-H4 表达。此外，管腔型雄激素受体（LAR）亚型常缺乏 B7-H4 表达；在非 LAR 亚型中，B7-H4 和 IDO1 表达呈互斥关系。
展开英文摘要原文
BACKGROUND
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.
METHODS
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.
RESULTS
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 ( = - 0.509, p < 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 ( = - 0.354, p < 0.001).
CONCLUSIONS
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.
论文信息
- 作者
- Sanuki F、Mikami Y、Nishimura H、Fujita Y、Monobe Y、Nomura T、Taira N、Moriya T
- 第一作者单位
- Department of Pathology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.Japan
- 通讯作者单位
- Department of Pathology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. tmoriya@med.kawasaki-m.ac.jp.Japan
- 期刊
- Breast cancer (Tokyo, Japan)2023 Nov
- 原文标识
- PubMed 37642903 · DOI 10.1007/s12282-023-01498-7