Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing, China.
Front Immunol. 2024 Jan 26;15:1287632. doi: 10.3389/fimmu.2024.1287632. eCollection 2024.
Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis.
We collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis.
The cytokine response in peripheral CD4 T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified.
We comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.
结直肠癌（CRC）是全球第三大常见癌症，其发病率和死亡率都很高。CRC 的发生是通过传统的腺瘤-癌途径和锯齿状途径。传统的辅助性 T 细胞（Th）和固有淋巴细胞（ILC）在维持肠道稳态方面发挥着重要作用。然而，这两种主要淋巴细胞群及其相关细胞因子对 CRC 发展的贡献尚不清楚。因此，我们旨在分析结直肠癌变过程中的外周淋巴细胞谱。
我们同时采集了 86 份血样，病理学家通过苏木精和伊红染色确认了各种病理情况（即 HP、腺瘤和癌）的存在。从体检中心招募了 10 名健康供体作为健康对照（HCs）。我们对来自不同病理条件和 HCs 的患者的外周血单个核细胞进行了流式细胞术，并对细胞因子（白细胞介素 2、白细胞介素 4、白细胞介素 5、白细胞介素 13、白细胞介素 17A、白细胞介素 17F、白细胞介素 22、干扰素-γ 和肿瘤坏死因子-α）进行了定量分析。我们还分析了来自结直肠癌变不同阶段的组织样本的已发表单细胞 RNA 序列数据。
在外周 CD4 T 细胞中，细胞因子反应在癌过程中上调。在腺瘤和癌阶段，外周调节性 T 细胞（Treg）的频率增加。而滤泡辅助性 T 细胞（Tfh）细胞比例在腺瘤和癌过程中下调。因此，Th 细胞亚群，特别是 Treg 和 Tfh 细胞，参与了结肠疾病。此外，还明确了 HP 中的免疫谱特征。
我们全面分析了结直肠癌进展过程中循环 ILC 和适应性 T 淋巴细胞亚群。我们的结果显示了免疫谱特征，并支持 Th 亚群，特别是 Treg 和 Tfh 细胞群，参与了结肠疾病。这些发现显著增强了我们对 CRC 及其癌前病变免疫机制的理解。进一步研究 Treg 和 Tfh 细胞在结直肠疾病发展中的功能将为监测和预防 CRC 发展提供潜在的治疗靶点。
