Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Front Cell Infect Microbiol. 2023 Mar 7;13:1101291. doi: 10.3389/fcimb.2023.1101291. eCollection 2023.
BACKGROUND & AIMS: (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated.
The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes.
Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8 and FoxP3 regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner.
FN enhanced the suppressive immune microenvironment with high depletion of CD8 T cells and enrichment of FoxP3 regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.
（FN）通过调节抗肿瘤免疫反应在结直肠癌的发生和发展中发挥关键作用。然而，FN 对肿瘤微环境中免疫调节的影响尚未完全阐明。
使用定量聚合酶链反应测量 99 例 III 期 CRC 肿瘤组织中 FN 的丰度。使用共识分子亚型（CMS）、基因本体论（GO）分析和 FN 丰度背景下个体免疫细胞类型的去卷积评估和注释基因表达谱。使用流式细胞术分析从人肿瘤组织中分离的肿瘤浸润 T 细胞的免疫谱。在存在或不存在 FN 的情况下刺激肿瘤浸润 T 细胞，以确定 FN 对免疫细胞表型的直接影响。
基因表达谱、CMS 组成、免疫细胞亚型丰度和生存结果因 FN 感染而异。我们发现，FN 感染与 III 期 CRC 患者无病生存率和总生存率降低有关。FN 感染与肿瘤微环境中 T 细胞耗竭以及耗竭的 CD8 和 FoxP3 调节性 T 细胞富集有关。肿瘤中 FN 的存在与以 T 细胞依赖性方式具有抑制性肿瘤微环境相关。
FN 通过耗尽 CD8 T 细胞并增加 FoxP3 调节性 T 细胞在人类结直肠癌病例中增强了抑制性免疫微环境。我们的研究结果表明 FN 与适应性免疫之间存在潜在关联，具有生物学和预后意义。
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