Study Finds Gut Microbes May Promote Immune Responses Against Colorectal Cancer
Colorectal cancer is the third leading cancer-related cause of death worldwide, accounting for 774,000 deaths in 2015, according to the World Health Organization. Now, a study presented at the third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science Into Survival, held in Mainz/Frankfurt, Germany, on September 6–9, 2017, is shedding light on the role gut microbes play in promoting an immune response against colorectal cancer cells. The study (Abstract B250) by Cremonesi et al investigated the interaction between the gut microbiota and chemokines in promoting colorectal cancer infiltration by immune cells and how this influences the clinical course of the disease; they found that gut microbiota stimulate chemokine production that recruits T cells to the tumor, which may be associated with improved outcomes.
Study Methodology and Findings
The researchers assessed the expression of chemokines, chemokine receptors, and immune cell markers in a cohort of 62 freshly excised human colorectal cancers and adjacent healthy colonic tissue and evaluated bacterial load, chemokine expression, and T-cell recruitment into intraperitoneal and intracecal colorectal cancer xenografts in vivo.
The researchers found that colorectal cancer infiltration by immune cells was associated with defined chemokine gene signatures, including CCL5, CXCL9, and CXCL10 for cytotoxic T lymphocytes and T-helper 1 cells, and CCL17, CCL22, and CXCL12 for T-helper 1 and regulatory T cells. Most of these chemokine genes were expressed by tumor cells upon exposure to gut bacteria in vitro and in vivo. The chemokine expression levels were significantly higher in orthotopic intracecal xenografts than in intraperitoneal tumors and were drastically reduced by antibiotic treatment of tumor-bearing mice, suggesting a role for commensal bacteria in chemokine induction in tumor cells. The extent of T-cell infiltration into tumor xenografts significantly correlated with bacterial loads.
Role of Gut Microbes in Colorectal Cancer Progression
“That gut microbes play a role in colorectal cancer progression might appear like the 'Columbus egg,'” said Eleonora Cremonesi, PhD, a postdoctoral fellow at the University of Basel in Switzerland and the leading author of this study, in a statement. “However, mechanisms involved in the generation of the peculiar microenvironment of colorectal cancer and in the interaction between cancer and immune cells are still largely unclear. Our findings may open the way toward the development of new treatments aimed at modifying the gut flora to promote the infiltration of colorectal cancers by lymphocytes displaying antitumor effects.”
In a press briefing at the International Cancer Immunotherapy Conference, Cornelis J.M. Melief, MD, PhD, Head of the Department of Immunohematology and Blood Transfusion at the Leiden University Medical Center in The Netherlands, provided his insight into the study results. “The tonus of our immune system in each person to a large extent is determined by the microbial composition and load that each person has, which is unique for each person. It is, for example, very important to make sure that a patient doesn’t get antibiotic treatment to deplete their possibly favorable microbiota during the immunotherapy,” said Dr. Melief. “So, bad and good bacteria have now been identified as a prospect of … bacterial transplantation prior to immunotherapy. I think it’s a very interesting field in itself.”
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