肿瘤细胞治疗研究
英文原题：IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions.
IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions.
我们分析了IMMUNOREACT 1和2多中心观察性研究（624例患者）中存在的25例异时性RC的黏膜免疫微环境。
Lynch 综合征很少与直肠癌（RC）相关，因此，异时性 RC 鲜有研究。本研究旨在分析散发性与异时性 RC 的黏膜免疫微环境。我们分析了 IMMUNOREACT 1 和 2 多中心观察性研究（624 例患者）中存在的 25 例异时性 RC 的黏膜免疫微环境。通过免疫组织化学回顾性检测了一组免疫标志物：CD3、CD4、CD8、CD8b、Tbet、FoxP3、PD-L1、MSH6 和 PMS2 以及 CD80。对单细胞悬液进行流式细胞术，以确定作为抗原呈递细胞（表达 CD80、CD86、HLA-ABC）的上皮细胞（pan-cytokeratin）比例，以及活化 CD8+ T 细胞（CD8+ 且 CD28、CD38 阳性）的比例、抑制性 T 细胞（CD3+ CTLA-4+）、活化 CD4+ T 辅助细胞（CD4+ CD25+）和活化 T 调节细胞（CD4+ CD25+ FoxP3+）的比例。在患者中未观察到错配修复基因缺陷。既往结直肠腺瘤病史在异时性 RC 中显著更为常见。在健康上皮细胞中，异时性 RC 患者的 HLA-ABC 表达显著更高。在未接受治疗的异时性 RC 患者中，与非异时性癌症患者相比，观察到循环淋巴细胞水平以及 RC 周围健康黏膜中 CD3+ T 细胞浸润显著更低。我们的研究支持以下假说：异时性 RC 可发生于全身和局部免疫系统较弱的患者的癌化场中。RC 的特殊部位使得错配修复基因缺陷在异时性癌症发生中的相关性较低。
Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.
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