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01-01-2020 | Respiratory Microbiota | Original Article

Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers

Authors: Tomohiro Kikuchi, Kosaku Mimura, Mai Ashizawa, Hirokazu Okayama, Eisei Endo, Katsuharu Saito, Wataru Sakamoto, Shotaro Fujita, Hisahito Endo, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze, Shinji Ohki, Kazunori Shimada, Kiyoshi Yoshimura, Takuya Tsunoda, Koji Kono

Published in: Cancer Immunology, Immunotherapy | Issue 1/2020

Abstract

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^lowCD45RA⁺ Tregs were significantly reduced (p = 0.02), FOXp3^lowCD45RA⁻ 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^highCD45RA⁻ 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.

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Title: Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers
Authors: Tomohiro Kikuchi
Kosaku Mimura
Mai Ashizawa
Hirokazu Okayama
Eisei Endo
Katsuharu Saito
Wataru Sakamoto
Shotaro Fujita
Hisahito Endo
Motonobu Saito
Tomoyuki Momma
Zenichiro Saze
Shinji Ohki
Kazunori Shimada
Kiyoshi Yoshimura
Takuya Tsunoda
Koji Kono
Publication date: 01-01-2020
Publisher: Springer Berlin Heidelberg
Keywords: Respiratory Microbiota
Colorectal Cancer
Colorectal Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 1/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02433-6

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