Research News

Patients with early-onset colorectal cancer (CRC) employ a broader variety of immune cells called T cells to attack tumors than average-onset patients, according to new Cleveland Clinic research. The Journal of the National Cancer Institute paper comes from the laboratory of Stephanie Schmit, PhD, MPH and identifies key differences in how patients’ immune systems respond to early-onset colorectal cancer ( < 50 years old) versus average-onset CRC (≥ 60 years). This study reinforces that these seemingly similar cancers may have different underlying causes and highlights the complexity of the interactions between cancer cells and the immune system.  

Study first author Ya-Yu Tsai, PhD, is a project scientist in Dr. Schmit’s lab who specializes in genetics and in the immune response to colorectal cancer. After co-authoring a paper about how genetic factors help determine an individual’s immune response to CRC, Dr. Tsai next investigated immune responses in individuals diagnosed at an early age versus an average age of onset. 

Dr. Tsai collaborated with clinicians at Cleveland Clinic’s Center for Young- Onset Colorectal Cancer to generate and analyze data on solid tumors from 242 patients who underwent surgery to treat their colorectal cancer. She used a technique called immunosequencing to identify the T-cell receptors (molecules on immune cells that help to recognize tumor cells) that are intermixed with tumor cells. This method allowed the research team to see how many and what types of T cells the patients’ immune systems employed to attack the cancer. 

Early-onset CRC patients expressed more types of T-cell receptors than average-onset patients. The team analyzed data from a broader team of national and international collaborators to confirm the findings in an independent sample. 

“A more diverse immune response suggests that the development of and response to early-onset CRC may be influenced by a unique set of factors compared to average-onset CRC,” says Dr. Schmit, Vice Chair of Genomic Medicine. “A more diverse immune response could also impact an individual's prognosis and their response to treatment.” 

According to Drs. Schmit and Tsai, having a more diverse response may spread the immune system thin and lead to a weaker overall response to therapy than a response with of one or two immune cell types that the patient’s immune system makes specifically to target the cancer. 

“We hope to inspire other investigators to pay more attention to the details of tumor immune responses in early-onset patients to further examine a potentially different etiology and response to the disease,” says Dr. Tsai. “With more data, we could begin to correlate these responses with possible treatments and clinical outcomes to tailor therapies for each colorectal cancer patient.” 

The Schmit Lab will continue collaborating with the Center for Young-Onset Colorectal Cancer to investigate tumor immune responses and immune heterogeneity in more diverse patient populations, including the Hispanic/Latino community.