Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
Pathobiology. 2020;87(3):179-192. doi: 10.1159/000505756. Epub 2020 Feb 21.
B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive.
We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ hybridization (ISH) and immunohistochemistry in 10 pairs of breast cancer and matched normal tissues. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed in tissue microarray slides containing 198 breast cancer samples. Association of B7-H3 and B7-H4 expression with survival was verified using the publicly accessible BreastMark tool.
B7-H3 and B7-H4 mRNA expression were significantly higher in breast cancer samples in the TCGA dataset than in normal breast tissues in the GTEx dataset. RNAscope ISH and immunohistochemistry showed that B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in cancer cells. Expression of B7-H3 and B7-H4 tended to be associated with low-density scores of stromal tumor-infiltrating lymphocytes (TILs) as well as molecular subtypes. Expressions of B7-H3 and B7-H4 were negatively correlated with stromal CD3+ and CD8+ T cell infiltration density. B7-H3 and B7-H4 expression was not associated with survival, which was verified by BreastMark analysis.
Expression levels of B7-H3 and B7-H4 were independent of clinical outcomes of breast cancer. There was an inverse relationship between the expression of B7-H3 and B7-H4 in breast cancer and the density of stromal TILs and CD8+ T lymphocytes. This inverse relationship may represent a promising target in the field of breast cancer immunotherapy.
B7-H3 和 B7-H4 蛋白在乳腺癌组织中表达，但它们与肿瘤免疫监测和乳腺癌结局的关系尚无定论。
我们首先在 Genotype-Tissue Expression (GTEx) 和 The Cancer Genome Atlas (TCGA) 数据库中检测了 B7-H3 和 B7-H4 的 mRNA 表达。然后，通过 RNAscope 原位杂交 (ISH) 和 10 对乳腺癌和配对正常组织的免疫组化评估了 mRNA 和蛋白表达。在包含 198 例乳腺癌样本的组织微阵列载玻片上进行了 B7-H3、B7-H4、CD3 和 CD8 的免疫组织化学染色。使用可公开访问的 BreastMark 工具验证了 B7-H3 和 B7-H4 表达与生存的关联。
TCGA 数据集的乳腺癌样本中 B7-H3 和 B7-H4 mRNA 表达明显高于 GTEx 数据集中的正常乳腺组织。RNAscope ISH 和免疫组化显示 B7-H3 和 B7-H4 mRNA 和蛋白似乎主要在癌细胞中表达。B7-H3 和 B7-H4 的表达倾向于与基质肿瘤浸润淋巴细胞 (TIL) 的低密度评分以及分子亚型相关。B7-H3 和 B7-H4 的表达与基质 CD3+和 CD8+T 细胞浸润密度呈负相关。B7-H3 和 B7-H4 的表达与生存无关，这一点通过 BreastMark 分析得到了验证。
B7-H3 和 B7-H4 的表达水平与乳腺癌的临床结局无关。B7-H3 和 B7-H4 在乳腺癌中的表达与基质 TIL 和 CD8+T 淋巴细胞密度呈负相关。这种负相关关系可能代表了乳腺癌免疫治疗领域的一个有前途的靶点。
