Immune clues in the tumor: how T cells may help predict colon cancer survival

When we think of the immune system, we usually picture it fighting off colds and the flu. But what if it could also help fight cancer? A new study suggests that's exactly what's happening specifically in colorectal cancer (CRC). And the findings may one day help doctors predict outcomes and even tailor treatments for patients more effectively.

T cells, a key part of the immune system, can recognize and kill cancer cells, acting like the body's own internal defense squad. Most past studies lumped all T cells together and treated them as a single group. That’s a bit like judging a football team’s performance based only on how many players were on the field, without knowing what positions they played. This study, on the other hand, took a deep dive into the “positions” of these immune cells—their types and locations.

T cells are a type of white blood cell that helps defend the body against disease. They come in many flavors. Some are “naive,” T cells, standing by to respond to unfamiliar threats. Others are “memory” trained to recognize and quickly react to past invaders. Then there are “regulatory” T cells, which help keep the immune response in check, so it doesn't mistakenly harm healthy tissue.

A recently published study in Cancer Epidemiology, Biomarkers & Prevention, led by Drs. Claire Thomas, Amanda Phipps and their team, dove into the immune “lineup” inside tumors, focusing on T cells. But instead of just looking at how many T cells were present, they zoomed in to see which types of T cells were there, and where in the tumor they were located.

To do this, the research team turned to a cutting-edge technique called multiplex immunofluorescence. It’s a mouthful, but here’s the gist: it allows scientists tag different immune cells with fluorescent markers, kind of like highlighting lines in a book—except the “book” is a slice of tumor tissue, and the “highlighters” reveal which immune cells are present and where they’re hanging out. Using this technique, they studied more than 1,100 tumor samples from participants enrolled in large-scale health studies. With this approach, they could distinguish between several types of T cells and determine whether they were located in the epithelial (tumor core) or stromal (surrounding support tissue) regions. This level of detail is a game-changer.

As Dr. Thomas explained, “The immune landscape of colorectal cancer is complex, involving numerous cell subsets with diverse roles and, potentially, distinct relationships to CRC survival.” This wasn’t a manual process—trying to identify and count millions of cells by hand would be like trying to watch every player in hundreds of football games at once, with no replays. Instead, the team used machine learning algorithms to scan and analyze millions of immune cells across all those samples. In the end, they identified over half a million T cells and then dug into how both the number and the location of those cells were linked to survival.

The researchers found that “higher densities of CD3⁺CD4⁺ and CD3⁺CD8⁺ naive, memory, and regulatory T cells in both tumor epithelial and stromal regions were significantly associated with better CRC-specific survival,” said Dr. Thomas. In simple terms, patients with more of these specialized immune cells lived longer. But it wasn’t just about quantity; location mattered, too. T cells found in both the tumor’s core (the epithelial region) and its surrounding support tissue (the stromal region) were particularly associated with better outcomes. That’s what sets this study apart: it shows that survival isn’t only tied to how many immune cells are present, but also to which ones—and where they are.

“This study raises questions about what other components of the tumor immune microenvironment may potentially have differential roles on survival,” said Dr. Thomas. For example, how do other immune cells such as macrophages or natural killer (NK) cells, fit into the picture? And does the precise location of these cells within the tumor matter even more than we realize?

In the future, Dr. Thomas hopes “to better understand how the spatial location of T cells, beyond T cell densities described here, impact colorectal cancer survival”. Think of it as upgrading from a team photo to a full game replay, watching not just who was there, but what they were doing and where they moved.

For patients and their families, these findings are hopeful. They suggest that the body’s own immune system might help control, or even suppress cancer growth. With further research, it might become possible to assess a patient’s T cell profile and predict how they’re likely to respond to treatment or how aggressive their cancer might be. Even better, we may learn how to tweak the immune system to improve outcomes. In the meantime, this study is a powerful reminder that the immune system isn’t just a defense against germs. It’s also one of our greatest allies in the fight against cancer. And scientists like Dr. Thomas are helping us understand how to harness its full power.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Dr. Amanda Phipps contributed to this research.

This work was supported in part by NIH, and the Clinical Research Support and Specialized Pathology Divisional Cores at Fred Hutchinson Cancer Center.

Thomas, C. E., Takashima, Y., Buchanan, D. D., Wesselink, E., Qu, C., Hsu, L., Dias Costa, A., Gallinger, S., Grant, R. C., Huyghe, J. R., Thomas, S., Ugai, S., Zhong, Y., Matsuda, K., Ugai, T., Peters, U., Ogino, S., Nowak, J. A., & Phipps, A. I. (2025). Density of T cell subsets in colorectal cancer in relation to disease-specific survival. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 10.1158/1055-9965.EPI-25-0287. Advance online publication.