A hidden chain reaction in your gut silently reprograms your bone marrow to fuel colon cancer from everyday inflammation.

Story Snapshot

• Weill Cornell researchers uncovered how TL1A protein sparks a systemic immune cascade turning IBD inflammation into CRC tumors.
• Gut ILC3 cells release GM-CSF, triggering emergency neutrophil production that damages DNA in intestinal cells.
• Blocking TL1A reduces tumor-promoting neutrophil signatures in human IBD samples, pointing to new prevention strategies.
• Affects 3 million Americans with IBD, who face 2-3 times higher colon cancer risk at younger ages.

TL1A Protein Ignites the Inflammatory Cascade

Researchers at Weill Cornell Medicine pinpointed TL1A, an inflammatory protein elevated in IBD patients, as the trigger. TL1A activates gut-resident innate lymphoid cells type 3 (ILC3s). These cells release granulocyte-macrophage colony-stimulating factor (GM-CSF). This signal races to the bone marrow, launching emergency granulopoiesis. Neutrophils flood the gut, adopting a tumor-associated profile that shreds DNA in lining cells. Tumors form rapidly in preclinical models mimicking Crohn’s and ulcerative colitis.

Bone Marrow Reprogramming Links Gut to Cancer

The study reveals a systemic twist: gut signals reprogram distant bone marrow. Neutrophils arriving in the inflamed gut shift to TAN-like states, promoting tumorigenesis. Transferring these neutrophils alone sufficed to drive tumors in recipient mice. Human IBD samples mirrored this, with TAN signatures in precancerous dysplasia. TL1A blockade slashed the signature, validating the pathway. This gut-to-bone marrow axis explains why IBD doubles or triples CRC risk, with cancers striking younger and deadlier.

Why chronic gut inflammation can turn into colon cancerhttps://t.co/e9dN6jN0bb

— Wafik S. El-Deiry, MD, PhD, FACP (@weldeiry) January 25, 2026

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Historical Roots in IBD and Microbiota Dysbiosis

Doctors have linked chronic gut inflammation to colon cancer since the 1920s. IBD patients endure sustained neutrophil barrages and microbiota shifts. Dysbiosis unleashes toxins like Bacteroides fragilis toxin, firing up Wnt and NF-κB pathways for cell proliferation and DNA breaks. Short-chain fatty acids and bile acids tweak oncogenic signals including STAT3 and MAPK. Genetic TNFSF15 variants heighten TL1A, worsening IBD severity and CRC odds. These precedents set the stage for the new TL1A discovery.

Therapeutic Promise of Targeting the Axis

Anti-TL1A drugs, already in IBD trials, curb the neutrophil signature and hint at CRC prevention. Sílvia Pires, PhD, from Weill Cornell’s Longman Laboratory, calls this systemic process exciting for precision medicine. Clinicians could monitor TAN profiles to stratify high-risk IBD patients for early intervention. Pharma eyes expanding these blockers beyond inflammation control. Probiotics tackling dysbiosis offer complementary angles, aligning with common-sense prevention over reactive treatment.

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Implications for Millions at Risk

Over 2.4-3.1 million Americans battle IBD, facing a pro-tumor gut environment. Short-term, TAN signatures guide vigilant screening. Long-term, targeting TL1A, ILC3s, GM-CSF, or neutrophils could slash CRC incidence. Economic wins include averting costly cancer care; socially, IBD sufferers gain better lives without cancer dread. Preclinical strength shines, though human trials loom as the next hurdle. Conservative values favor these proactive, evidence-based shields against chronic disease burdens.

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Sources:

Why chronic gut inflammation can turn into colon cancer
IBD Linked to Colon Cancer Through TL1A-Driven Immune Pathway
Gut Microbiota Dysbiosis in Inflammatory Bowel Disease
Enterotoxigenic Bacteroides fragilis: A Rare but Relevant Cause of Diarrhea and Colitis