The study reveals that instead of one uniform group, there are two distinct subtypes of Treg cells in colorectal tumors that act as polar opposites.
Tale of Two T-Cells: Helpful vs. Harmful
In most cancers, Treg cells act like a shield for the tumor, preventing the immune system from attacking it. However, in colorectal cancer, the "helpful" subtype changes the narrative.
| Feature | Helpful Tregs (IL-10 Positive) | Harmful Tregs (IL-10 Negative) |
| Marker | Produces Interleukin-10 (IL-10) | Lacks IL-10; Expresses CCR8 |
| Location | Abundant in healthy tissue near the tumor | Found primarily inside the tumor |
| Action | Suppresses Th17 cells, which produce growth factors for the tumor | Suppresses CD8+ T cells, the body's natural "cancer killers." |
| Impact | Restrains tumor growth; linked to longer survival | Fuels tumor growth; linked to worse outcomes |
Why This Matters for Immunotherapy
About 80% to 85% of colorectal cancers are "microsatellite stable" (MSS), meaning they are largely resistant to current immunotherapies. This research identifies a specific vulnerability in these resistant tumors.
The Strategy: Selective Targeting via CCR8
The harmful, immunosuppressive Treg cells express high levels of a protein called CCR8. Because the "good" cells do not have this marker, scientists can use CCR8-depleting antibodies to:
- Eliminate the cells that hide the tumor from the immune system.
- Preserve the IL-10-positive cells that help keep the tumor from growing.
Broader Implications for "Barrier" Cancers
The research suggests this "two-subtype" pattern isn't unique to the colon. Similar divisions were found in cancers affecting barrier tissues—tissues constantly exposed to environmental stress and microbes, such as:
- Skin
- Stomach lining
- Mouth and throat
In these tissues, the immune system is already programmed to balance defense with repair, which explains why the "helpful" Tregs exist there to prevent over-inflammation.
A Note on Metastasis
Interestingly, the pattern changes if the cancer spreads. When colorectal cancer metastasizes to the liver, the harmful IL-10-negative cells dominate. In this specific context, removing all Treg cells—rather than being selective—actually helps shrink the tumors. This underscores the need for "context-specific" treatments depending on where the cancer is located.
"Discovery of two opposing subtypes of regulatory T cells in colorectal cancer shifts the paradigm. Because one subtype fuels the disease while the other restrains it, we must move toward 'surgical' immune therapies that can tell the two apart." — Dr. Alexander Rudensky, MSK
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