Immune Microenvironment Changes Could be Used to Detect Colorectal Cancer Earlier and Predict Risks

A recent study from Mass General Brigham investigates how the immune microenvironment evolves throughout the progression of colorectal cancer, with the goal of improving early detection and risk assessment. The research sheds light on the ways the immune system interacts with benign precancerous lesions in the colon, specifically focusing on the role of T cells as colorectal tissue transitions from normal to malignant. 

Colorectal cancer precursor lesions, which are noncancerous growths, can ultimately lead to cancer via conventional or serrated pathways. Gaining a better understanding of how the immune system responds to these lesions may not only advance scientific knowledge of cancer development but also have implications for future treatment options. To answer these questions, the Mass General Brigham team examined how T cells are distributed and behave during the progression from normal tissue to precancerous lesions and, eventually, to full-blown cancer.

Shuji Ogino, senior author of the study published in Cancer Immunology Research, described the group’s findings: “Our study revealed differences in the immune microenvironment based on T-cell infiltration patterns leading to the development of CRC.” The team worked with tumor samples collected over decades from participants enrolled in three large-scale prospective cohort studies. Using fluorescent assays and advanced imaging, together with machine learning, they analyzed 1,825 tissue samples, which included 790 precancerous lesions and 1,035 cases of colorectal cancer. Through this approach, the researchers identified and classified T cells based on their function, activation status, and spatial localization. 

One of the key observations was that T-cell infiltration changed considerably along the spectrum from healthy tissue, to precancerous growths, to established cancer. Variations in the types and densities of T cells offered insights into the potential of each lesion to progress, and the spatial arrangement of T cells appeared to play a role in how well the immune system could respond. In discussing the implications, Ogino said, “Understanding T cell patterns in precancerous lesions could help us detect CRC earlier, predict risks, and develop therapeutic approaches.”

The study also marks the beginning of a novel approach known as the prospective cohort incident-tumor biobank method (PCIBM), which enables longitudinal profiling of risk factors and tumor features over time. According to Ogino, “Such a comprehensive longitudinal study has never been conducted in human history. We are making history in this regard.”