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人肠道微生物组中厚壁菌门的丰度高与晚期结直肠癌的高免疫评分有关。

High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer.

机构信息

Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu City, Shiga, 520-2192, Japan.

Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama, Shiga, 5268580, Japan.

出版信息

Cancer Immunol Immunother. 2023 Feb;72(2):315-326. doi: 10.1007/s00262-022-03256-8. Epub 2022 Jul 22.

Abstract

INTRODUCTION

The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear.

PATIENTS AND METHODS

A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing.

RESULTS

The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated (P = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC.

CONCLUSION

Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.

摘要

简介

结直肠癌(CRC)的肿瘤微环境(TME)包括肠道微生物群、免疫细胞、血管生成因子和成纤维细胞,在癌症进展中起主要作用。免疫评分(IS)基于浸润肿瘤的免疫细胞,这些细胞是 CRC 的已知预后生物标志物。然而,CRC 中 IS、微生物群和其他 TME 因素之间的相互关系尚不清楚。

患者和方法

在日本滋贺医科大学医院检查了 94 例 CRC 患者。通过免疫组织化学评估原发性肿瘤中 CD3、CD8、CD31 和α-平滑肌肌动蛋白(α-SMA)的表达水平。根据 CD3 和 CD8 染色测定的结果计算 IS。通过扩增子测序检查 CRC 患者的微生物组。

结果

CRC 患者的α-SMA 和肿瘤浸润淋巴细胞的表达水平呈负相关(P=0.006)。高 IS 与 CRC 患者微生物组中lachnospiraceae 的丰度增加有关。

结论

淋巴细胞浸润原发性肿瘤的特征是癌症相关成纤维细胞密度降低,肠道微生物组中lachnospiraceae 家族富集,这可能影响 CRC 的进展。

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