New Therapeutic Targets Could Treat Colon Tumors, Inflammatory Bowel Disease

Scientists found that inhibiting certain immune system receptors could treat colon cancer and other diseases of the gastrointestinal tract.

Scientists from Tokyo University of Science have discovered a new therapy that targets dendrite cell immunoreceptors (DCIR), which could treat inflammatory bowel disease (IBD) and colorectal cancer. The team’s findings were published online in Cell Reports.1

IBD is inflammation of the gastrointestinal (GI) tractand is the umbrella term for Crohn disease and ulcerative colitis. Understanding the pathogenesis of IBD, a condition that often leads to colorectal tumors, could help decrease tumor formation, according to the study investigators.

Common symptoms of IBD include abdominal pain, persistent diarrhea, fatigue, and bloody stool.The disease is currently treated using biologics, corticosteroids, and some surgeries to remove damaged parts of the GI tract.2

Innate immune receptors recognize and respond to pathogens. Innate immune receptors also create local inflammation on injuries, recruit effector cells, contain local infections, and incite an adaptive immune response.3

C-type lectin receptors (CLR) are innate immune receptors that regulate gut microbiota and defend the body against pathogens. It is a catch-22, however, because they also cause IBD.1

CLRs are broken down into different immunoreceptors. The dendrite cell immunoreceptor (DCIR) is a type of CLR that maintains immune and skeletal systems homeostasis. Researchers do not know how DCIR contributes to intestinal immunity, but some studies have suggested to block it to boost immunity against colon tumors.

Tokyo University of Science professor, Yoichiro Iwakura, led a team in studying immunoreceptors and colon tumors. Using mice models, they examined colitis and colon tumor growth for mice deficient in DCIR.1

The researchers gave the mice cancer by feeding them contaminated water that contained a mix of a synthetic sulfated polysaccharide, dextran sodium sulfate (DSS), and a neurotoxic chemical, azoxymethane.

The mice with lower DCIR experienced less severe colorectal tumor growth. These DCIR-deficient mice also did not lose as much weight, nor did their colon have as much proinflammatory cell infiltration.

Researchers discovered that the antibody anti-NA2 reduced symptoms of the toxic DSS polysaccharide and prevented colorectal tumor growth by fighting against DCIR ligand asialo-biantennary-N-glycans (NA2).

“Our findings point to the fact that intestinal carcinogenesis and inflammation are facilitated by DCIR signaling, which points to the possibility that blocking DCIR might prevent ulcerative colitis and colon cancer,” Iwakura said in a press release. “Our results suggest that therapeutics targeting DCIR and its ligands could be used to effectively treat autoimmune diseases, IBD, and cancer, which have been traditionally difficult to treat,” Iwakura said.1

References

  1. Scientists uncover new therapeutic target for treating colorectal tumors. EurekAlert! Aug 2, 2022. Accessed on Aug 3, 2022. https://www.eurekalert.org/news-releases/960232
  2. Center for Disease Control and Prevention. What is IBD? CDC website. Accessed Aug 3, 2022. https://www.cdc.gov/ibd/what-is-IBD.htm#treatment
  3. National Library of Medicine.Receptors of the innate immune system. NLM website. https://www.ncbi.nlm.nih.gov/books/NBK27129/#:~:text=The%20innate%20immune%20system%20uses%20a%20diversity%20of%20receptors%20to,not%20found%20on%20host%20cells.Accessed Aug 3, 2022.