胃癌患者癌组织和外周血中 PD-L1 和 CTLA-4 阳性 T 细胞的预后意义及免疫抑制标志物表达的正相关性。
Prognostic significances of PD-L1- and CTLA-4-positive T cells and positive correlations of immunosuppressive marker expression between cancer tissue and peripheral blood in patients with gastric cancer.
机构信息
Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
出版信息
Front Immunol. 2023 Apr 21;14:1138743. doi: 10.3389/fimmu.2023.1138743. eCollection 2023.
INTRODUCTION
Although tumor, node, metastasis (TNM) staging has been used for prognostic assessment of gastric cancer (GC), the prognosis may vary among patients with the same TNM stage. Recently, the TNM-Immune (TNM-I) classification staging system has been used for prognostic assessment of colorectal cancer based on intra-tumor T-cell status, which is a superior prognostic factor compared with the American Joint Committee on Cancer staging manual. However, an immunoscoring system with prognostic significance for GC has not been established.
METHOD
Here, we evaluated immune phenotypes in cancer and normal tissues, then examined correlations between tissues and peripheral blood. GC patients who underwent gastrectomy at Seoul St. Mary's Hospital between February 2000 and May 2021 were included. We collected 43 peripheral blood samples preoperatively and a pair of gastric mucosal samples postoperatively, including normal and cancer mucosa, which did not influence tumor diagnosis and staging. Tissue microarray samples of GC were collected from 136 patients during surgery. We investigated correlations of immune phenotypes between tissues and peripheral blood using immunofluorescence imaging and flow cytometry, respectively. GC mucosa exhibited an increased number of CD4 T cells, as well as increased expression levels of immunosuppressive markers (e.g., programmed death-ligand-1 [PD-L1], cytotoxic T lymphocyte antigen-4 [CTLA-4], and interleukin-10), in CD4+ T cells and non-T cells.
RESULT
The expression levels of immunosuppressive markers were significantly increased in cancer tissues and peripheral blood mononuclear cells. In gastric mucosal tissues and peripheral blood of GC patients, similar immunosuppression phenotypes were observed, including increased numbers of PD-L1- and CTLA-4-positive T cells.
DISCUSSION
Therefore, peripheral blood analysis may be an important tool for prognostic assessment of GC patients.
简介
尽管肿瘤、淋巴结、转移（TNM）分期已被用于评估胃癌（GC）的预后，但具有相同 TNM 分期的患者预后可能存在差异。最近，基于肿瘤内 T 细胞状态的 TNM-免疫（TNM-I）分类分期系统已被用于结直肠癌的预后评估，与美国癌症联合委员会分期手册相比，这是一个更好的预后因素。然而，尚未建立用于 GC 的具有预后意义的免疫评分系统。
方法
在这里，我们评估了癌症和正常组织中的免疫表型，然后检查了组织和外周血之间的相关性。纳入 2000 年 2 月至 2021 年 5 月期间在首尔圣玛丽医院接受胃切除术的 GC 患者。我们在术前收集了 43 份外周血样本和一对胃黏膜样本，包括正常和癌症黏膜，这不会影响肿瘤诊断和分期。GC 组织微阵列样本是在手术期间从 136 名患者中收集的。我们使用免疫荧光成像和流式细胞术分别研究了组织和外周血之间免疫表型的相关性。GC 黏膜中 CD4+T 细胞数量增加，以及免疫抑制标记物（如程序性死亡配体-1[PD-L1]、细胞毒性 T 淋巴细胞抗原-4[CTLA-4]和白细胞介素-10）在 CD4+T 细胞和非 T 细胞中的表达水平也增加。
结果
免疫抑制标记物的表达水平在癌症组织和外周血单核细胞中显著增加。在 GC 患者的胃黏膜组织和外周血中，观察到类似的免疫抑制表型，包括 PD-L1 和 CTLA-4 阳性 T 细胞数量增加。
讨论
因此，外周血分析可能是评估 GC 患者预后的重要工具。
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