Research News

A global collaboration with lead authors from Cleveland Clinic has identified genetic factors that could affect how well our immune systems respond to colorectal cancer. The BMC Genomics paper is the largest and most comprehensive analysis of population-based studies into the topic. 

One factor that predicts a patient's prognosis following a diagnosis of colorectal cancer is their immune response to the disease, measured by their immune cells' ability to recognize cancers and destroy the affected cells. Studies show that the more robust someone's immune system is in the area of the tumor, the more likely they are to respond to checkpoint inhibitor immunotherapy and the better their overall prognosis. Beyond important molecular features called tumor mutational burden and microsatellite instability, it remains unclear what factors influence peoples' immune responses to cancer. 

"The immune system is the body's natural surveillance system. It's designed to identify and remove cancer cells," says study co-first author Stephanie Schmit, PhD, Vice Chair of the Genomic Medicine Institute. "The biomedical field still doesn't fully understand why the immune system varies so much across individuals diagnosed with colorectal cancer, even those diagnosed at the same stage. This knowledge could help us learn how to better leverage our own immune systems to enhance recognition and clearance of cancerous cells." 

With an ultimate goal of improving patient outcomes, Dr. Schmit worked with researchers from across the globe, including Ya-Yu Tsai, PhD, project scientist in the Schmit Lab, Stephen Gruber, MD, PhD, MPH, medical oncologist and vice president of the City of Hope National Medical Center. Together, they analyzed data from over 3,600 patients who were diagnosed with colorectal cancer, using DNA samples and clinical information to better understand how inherited genetics influence our response to the disease. 

The team found multiple inherited variants throughout the patients' genomes that influenced how responsive their immune cells were to colorectal cancer. Further research will help determine how to leverage these mutations for potential prevention, diagnostic and/or treatment purposes. 

Dr. Schmit hopes her team's study will serve as a call to action for other colorectal cancer researchers and physicians to analyze and share patient immune profiling data with the rest of the scientific community. 

"Our analyses combine all of the currently available data of this type that are known to exist, but we still need more numbers to replicate these findings before we can move forward and identify the most important genes contributing to the immune response to colorectal cancer and its treatment," she says.

Since this research project began almost ten years ago, several of Dr. Schmit's colleagues and collaborators have been collecting their own data. The power of team science and collaboration will be critical to move the field forward. 

"I started this project as a postdoctoral researcher in Dr. Gruber's lab and could not have completed this work without his support or the support of some great global collaborators," she says. "Working together and sharing data is the only way to make population science discoveries that inform medical advances and improve patient outcomes and care."