Macrophage-Induced Senescent Cancer-Associated Fibroblasts Promote SASP-Mediated Chemoresistance in Colorectal Cancer.

Macrophage-induced IL1B-IL1R1 signaling promotes senescent CAFs that mediate chemoresistance in colorectal cancer.

• Why it matters: Understanding how the tumor microenvironment contributes to therapy resistance is crucial for improving colorectal cancer outcomes, as CAF senescence impacts treatment efficacy.
• What they did: A machine learning model identified senescent CAFs in single-cell RNA data, revealing their correlation with poor chemotherapy response; functional studies confirmed macrophage-derived IL1B triggers CAF senescence via IL1R1, promoting SASP-mediated resistance.
• The result: Targeting the IL1B-IL1R1 pathway may enhance chemotherapy effectiveness by preventing CAF senescence and SASP secretion, offering a potential therapeutic strategy in colorectal cancer.