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Abstract：
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.
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.
摘要：
结直肠癌（CRC）是全球第三大流行癌症，其发病率和死亡率都很高。结直肠癌的发生是通过常规的腺瘤到癌和锯齿状途径发生的。常规辅助性T细胞（Th）和先天淋巴样细胞（ILC）在维持肠道稳态中起着至关重要的作用。然而,这两种主要淋巴细胞群及其相关细胞因子对CRC发生的贡献尚不清楚.因此,我们旨在分析结直肠癌发生过程中的外周血淋巴细胞谱。
■我们同时采集了86份血样,病理学家证实了各种病理状况的存在(即，惠普,腺瘤，和癌）使用苏木精和伊红染色。从体检中心招募10名健康供体作为健康对照(HCs)。我们对从各种病理状况和HCs患者收集的外周血单个核细胞进行了流式细胞术，和细胞因子（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）进行定量。我们还分析了来自结直肠癌发生不同阶段的组织样本的已发表的单细胞RNA序列数据。
■在癌变过程中,外周CD4+T细胞中的细胞因子应答上调。在腺瘤和癌分期中，外周调节性T细胞（Tregs）的频率增加。而滤泡辅助性T细胞（Tfh）比例在腺瘤和癌过程中下调。因此，Th细胞亚群，尤其是Tregs和Tfh细胞，与结肠疾病有关。此外，阐明了HP的免疫学特征。
■我们全面分析了大肠癌进展中的循环ILC和适应性T细胞淋巴细胞亚型。我们的结果显示了免疫学特征，并支持Th亚群的参与，特别是Treg和Tfh细胞群，在结肠疾病中。这些发现极大地增强了我们对CRC及其癌前病变的免疫机制的理解。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。
■我们同时采集了86份血样,病理学家证实了各种病理状况的存在(即，惠普,腺瘤，和癌）使用苏木精和伊红染色。从体检中心招募10名健康供体作为健康对照(HCs)。我们对从各种病理状况和HCs患者收集的外周血单个核细胞进行了流式细胞术，和细胞因子（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）进行定量。我们还分析了来自结直肠癌发生不同阶段的组织样本的已发表的单细胞RNA序列数据。
■在癌变过程中,外周CD4+T细胞中的细胞因子应答上调。在腺瘤和癌分期中，外周调节性T细胞（Tregs）的频率增加。而滤泡辅助性T细胞（Tfh）比例在腺瘤和癌过程中下调。因此，Th细胞亚群，尤其是Tregs和Tfh细胞，与结肠疾病有关。此外，阐明了HP的免疫学特征。
■我们全面分析了大肠癌进展中的循环ILC和适应性T细胞淋巴细胞亚型。我们的结果显示了免疫学特征，并支持Th亚群的参与，特别是Treg和Tfh细胞群，在结肠疾病中。这些发现极大地增强了我们对CRC及其癌前病变的免疫机制的理解。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。
