Colorectal cancer precursor lesions are benign growths that can develop into colorectal cancer (CRC) over time, through either a conventional or serrated pathway.

Understanding how the immune system reacts to these precursor lesions could further the understanding of CRC development as well as potential treatment options.

To this end, a new study from researchers at Mass General Brigham explores T cell behavior and distribution in the colorectal area as cancer progresses, detecting distinct patterns associated with progression.

Results are published in Cancer Immunology Research.

“Our study revealed differences in the immune microenvironment based on T-cell infiltration patterns leading to the development of CRC,” said senior author Shuji Ogino, MD, PhD, MS, American Cancer Society Professor and the Chief of the Molecular Pathological Epidemiology Program in the Mass General Brigham Department of Pathology. “This new knowledge has the potential to help us detect CRC earlier by predicting risk.”

The team used tissue from tumors that had occurred over decades in people who were followed as part of three large-scale prospective cohort studies to perform fluorescent assays targeting proteins in the immune system.

Using high-tech imaging platforms and machine learning, they were able to analyze 1,825 tissue samples, including 790 precancerous lesions and 1,035 with CRC. With these samples, the researchers identified T cells and categorized them by function, activation status and location. 

They found that T-cell infiltration varied significantly across the spectrum from normal tissue to precancerous lesions to cancer.

Differences in T cell types and densities indicated which precancerous lesions may be more likely to progress while spatial organization of T cells appeared to influence the effectiveness of the immune response.

“Understanding T cell patterns in precancerous lesions could help us detect CRC earlier, predict risks, and develop therapeutic approaches,” said Ogino.

“Much beyond that, this study is just the beginning of our prospective cohort incident-tumor biobank method (PCIBM)-based study of long-term, time-varying risk factors and tumor profiling of both colorectal precancers and cancers together. Such a comprehensive longitudinal study has never been conducted in human history. We are making history in this regard.”

Source: Mass General Brigham