Department of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Ksatowice, Poland.
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 19 Jordana, 41-800 Zabrze, Poland.
Cells. 2023 Mar 10;12(6):861. doi: 10.3390/cells12060861.
The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.
基于免疫检查点抑制剂的免疫疗法目前仅限于微卫星不稳定肿瘤,约占所有 CRC 病例的 15%。有一些新的免疫检查点属于 B7 家族,包括 B7H4。B7H4 的表达与所谓的“冷肿瘤”有关,其功能与各种免疫细胞群的下调有关。我们的研究旨在探讨 B7H4 的表达是否依赖于 CRC 的微卫星状态,并阐明 B7H4 表达发生的免疫学背景。我们招募了 167 名患者参与研究。我们从肿瘤组织和健康相邻组织中制备匀浆,以评估 B7H4 水平和 Bio-Plex Pro Human 48 细胞因子面板。我们通过免疫组织化学方法评估肿瘤的微卫星状态、B7H4 表达、CD8+T 细胞群体以及 H+E 染色载玻片上的 TILs 和芽生。我们使用在线可用数据库进一步探索 B7H4 的生物学特征。B7H4 的表达在微卫星稳定的肿瘤中更为频繁,与 TILs 呈负相关。B7H4 与抗肿瘤免疫抑制 iTME 呈正相关,从而有助于 CRC 中的免疫抑制环境。