Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
Department of Biomedical, Experimental and Clinical Sciences "Mario Serio" University of Florence, Florence, Italy.
Front Immunol. 2021 Jan 8;11:573158. doi: 10.3389/fimmu.2020.573158. eCollection 2020.
Gut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota-immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.
In this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.
CRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: , , , , and . Finally, the abundance of spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, spp. presence negatively correlated with IL-9.
Our data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host's commensal microorganisms. Indeed, we document, for the first time, that spp. and spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.
肠道微生物群（GM）可以通过产生免疫刺激性和/或免疫抑制性细胞因子来调节免疫反应，从而支持结直肠癌（CRC）的进展。IL-9 的作用是典型的，因为它既可以促进血液恶性肿瘤的肿瘤进展，也可以抑制实体癌的肿瘤发生。因此，我们研究了健康和肿瘤黏膜中的微生物群-免疫轴，重点关注细胞因子谱与 GM 特征之间的相关性。
在这项观察性研究中，我们收集了 2018 年在意大利佛罗伦萨卡雷吉大学医院接受手术的 45 名 CRC 患者的肿瘤（CRC）和健康（CRC-S）黏膜样本。首先，我们描述了组织浸润淋巴细胞亚群的特征和 GM 组成。随后，我们使用 Dirichlet 多项回归评估了 CRC 和 CRC-S 的分子炎症反应，并将该谱与 GM 组成相关联。
CRC 样本显示 Th17、Th2 和 Tregs 的百分比更高。此外，CRC 组织显示出显著更高水平的 MIP-1α、IL-1α、IL-1β、IL-2、IP-10、IL-6、IL-8、IL-17A、IFN-γ、TNF-α、MCP-1、P-选择素和 IL-9。与 CRC-S 相比，CRC 样本还显示出显著更高水平的以下属： 、 、 、 、 。最后，CRC 样本中 spp.的丰度与 IL-17A 呈负相关，与 IL-9 呈正相关。相反， spp.的存在与 IL-9 呈负相关。
我们的数据巩固了抗肿瘤免疫损伤以及与健康黏膜对应物相比肿瘤微环境中独特的微生物群谱的存在。将 CRC 的细胞因子谱与 GM 组成相关联，我们证实了免疫反应和宿主共生微生物之间存在双向串扰。事实上，我们首次记录到 spp.和 spp.分别与 IL-9 呈正相关和负相关，而 IL-9 在 CRC 发展中的作用仍存在争议。
