Zhang Hexun1, Toru Miyake2, Takeru Maekawa1, Haruki Mori1, Daiki Yasukawa1, Masashi Ohno3,4, Atsushi Nishida4, Akira Andoh4, Masaji Tani1. 1. Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu City, Shiga, 520-2192, Japan. 2. Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu City, Shiga, 520-2192, Japan. myk@belle.shiga-med.ac.jp. 3. Department of Gastroenterology and Hepatology, Nagahama City Hospital, Nagahama, Shiga, 5268580, Japan. 4. Department of Intestinal Medicine, Shiga University of Medical Science, Otsu, Japan.
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.
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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