Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers
Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers
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DOI：
10.1007/s00262-019-02433-6
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发表时间：
2020-01-01
影响因子：
5.8
通讯作者：
Kono, Koji
中科院分区：
文献类型：
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作者：
Kikuchi, Tomohiro;Mimura, Kosaku;Kono, Koji
最近有几篇文章报道，某些结肠微生物群可以提高癌症免疫治疗的疗效。为了开发新的治疗策略，包括结直肠癌（CRC）的免疫治疗，我们评估了CRC中肿瘤浸润免疫细胞（TIIC）亚群与肠道微生物群之间的相关性。方法收集新鲜手术切除标本、福尔马林固定石蜡包埋全组织样本和粪便样本。使用流式细胞术分析手术切除标本中的TIIC，包括Tcl 3、Th 17细胞和肿瘤相关巨噬细胞（TAM）。使用IHC分析全组织样品中的FOXp 3、CD 8、CD 163和磷酸化STAT 1阳性TIIC，并且使用16 S宏基因组测序分析粪便样品中的肠道微生物群。评估正常粘膜和肿瘤样品中的TIIC亚群，并分析TIIC亚群与肠道微生物群之间的相关性。结果肿瘤组织中FOXp 3（low）CD 45 RA（+）T细胞亚群显著减少（p = 0.02），FOXp 3（low）CD 45 RA（-）T细胞亚群显著增加（p = 0.006），M1 TAM显著减少（p = 0.03）。拟杆菌门（Bacteroidetes）和粪杆菌门（Firmicutes）在具有高数量的TcB和明显高分布的FOXp 3（高）CD 45 RA（-）TcB（其为效应TcB）的患者中增加。粪杆菌、瘤胃球菌科、真杆菌（厚壁菌门）和拟杆菌在M1 TAM分布较高的患者中增加。结论结直肠癌患者肿瘤微环境中的免疫应答受到抑制，其机制可能与肿瘤微环境中T淋巴细胞的增加和M1 TAM的减少有关，肠道菌群可能参与了免疫抑制。
Background Several articles have recently reported that certain colon microbiota can improve the efficacy of cancer immunotherapy. To develop new treatment strategies, including immunotherapy for colorectal cancer (CRC), we evaluated the correlations between subpopulations of tumor-infiltrating immune cells (TIICs) and intestinal microbiota in CRC. Methods Fresh surgically resected specimens, formalin-fixed paraffin-embedded whole tissue samples, and stool samples were collected. TIICs including Tregs, Th17 cells and tumor-associated macrophages (TAMs) in the surgically resected specimens were analyzed using flow cytometry. FOXp3, CD8, CD163, and phosphorylated-STAT1-positive TIICs in the whole tissue samples were analyzed using IHC, and intestinal microbiota in the stool samples was analyzed using 16S metagenome sequencing. TIICs subpopulations in the normal mucosa and tumor samples were evaluated, and the correlations between the TIIC subpopulations and intestinal microbiota were analyzed. Results FOXp3(low)CD45RA(+) Tregs were significantly reduced (p = 0.02), FOXp3(low)CD45RA(-) Tregs were significantly increased (p = 0.006), and M1 TAMs were significantly reduced in the tumor samples (p = 0.03). Bacteroides (phylum Bacteroidetes) and Faecalibacterium (phylum Firmicutes) were increased in the patients with high numbers of Tregs and clearly high distribution of FOXp3(high)CD45RA(-) Tregs, which are the effector Tregs. Faecalibacterium, Ruminococcaceae, Eubacterium (phylum Firmicutes), and Bacteroides were increased in patients with a high distribution of M1 TAMs. Conclusions The findings of the present study indicate that immune responses to tumors are suppressed in the tumor microenvironment of CRC depending on the increment of Tregs and the reduction of M1 TAMs and that intestinal microbiota might be involved in immunosuppression.