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

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

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Abbreviations

α-SMA:

Alpha-smooth muscle actin

CAF:

Cancer-associated fibroblast

CRC:

Colorectal cancer

CT:

Center of tumor

ECM:

Extracellular matrix

IM:

Invasive margin

LDA:

Linear discriminant analysis

LEfSe:

Linear discriminant analysis effect size

TIL:

Tumor-infiltrating lymphocyte

TME:

Tumor microenvironment

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Acknowledgements

We would like to thank Editage (www.editage.jp) for English language editing.

Funding

This work was supported by JSPS KAKENHI (Grant No. JP 19K16831 and JP 19K18081).

Author information

Authors and Affiliations

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

    Zhang Hexun, Toru Miyake, Takeru Maekawa, Haruki Mori, Daiki Yasukawa & Masaji Tani

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

    Masashi Ohno

  3. Department of Intestinal Medicine, Shiga University of Medical Science, Otsu, Japan

    Masashi Ohno, Atsushi Nishida & Akira Andoh

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  1. Zhang Hexun
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Contributions

TM described and designed this study. ZH acquired and analyzed the staining data. TM performed the next-generation sequencing analysis. TM, HM and DY collected the clinical samples and data and supported the analysis. TM and ZH made the drafting of this manuscript. AN, AA, HM, MO, and MT revised this article. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Toru Miyake.

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The authors have no conflicts of interest to disclose.

Ethical standard

The study complied with the ethical standards of the Declaration of Helsinki and was approved by the Ethics Committee of Shiga University of Medical Science (No. R2018-037).

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Hexun, Z., Miyake, T., Maekawa, T. et al. High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer. Cancer Immunol Immunother 72, 315–326 (2023). https://doi.org/10.1007/s00262-022-03256-8

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