A multi-disciplinary team of scientists from Northwestern Medicine and the University of Chicago investigated how lymphocytes, a type of white blood cell, increase inflammation in the body during colon cancer.
Of cancers that affect both men and women, colon cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women, according to the National Cancer Center at the National Institutes of Health. The number and type of lymphocytes that penetrate colon tumors affect the clinical outcomes of patients.
Dr. David Bentrem, Harold L. and Margaret N. Method Research Professor in Surgery, in collaboration with Mr. Khash Khazaie, a member of the Robert H. Lurie Comprehensive Cancer Center, previously identified a subset of regulatory T-cells, a type of lymphocyte, which cause an increase in inflammation in tumor samples from colon cancer patients.
In this new study, investigators combined data from patients who have colon cancer with mouse model studies of the disease to uncover the molecular mechanism behind the abnormal behavior of these T-cells. Their findings were recently published in Science Translational Medicine.
It is well known that varying numbers and types of lymphocytes infiltrate colon tumors, yet the role they play in cancer progression is not fully understood.
“More than half of the cells in solid tumors are not cancer cells, so we wanted to understand what these cells are doing and if they influence outcomes in colon cancer patients,” said Dr. Bentrem, who collaborated with Dr. Fotini Gounari, at the University of Chicago on the project. “We took tumors out of patients, isolated the lymphocytes, and were able to find subsets of regulatory T-cells that promoted inflammation. Next, the team focused on how these cells became pro-inflammatory.”
Using mouse models, they found that when high levels of beta-catenin, a regulatory protein, were expressed in T-cells, the mice were highly susceptible to colon cancer. This confirmed the role the protein plays in promoting the disease and shows how it contributes to intestinal inflammation and colon carcinogenesis in those with underlying colitis.
These results allow physicians to not only understand how inflammation in colon cancer occurs, but also provide insight into ways to create more effective treatment plans for patients.