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

Macrophage-induced senescent cancer-associated fibroblasts drive 78% chemoresistance in colorectal cancer via SASP factors IL6 and CXCL12.

• Why it matters: Understanding how the tumor microenvironment contributes to therapy resistance is vital for improving colorectal cancer outcomes, as current treatments often fail due to stromal influences.
• What they did: Researchers developed the Cellular Senescence Prediction Model (CSPM) using single-cell RNA sequencing to identify senescent CAFs and studied their role in chemoresistance across multiple preclinical models, focusing on IL1B-IL1R1 interactions.
• The result: Blocking the IL1B-IL1R1 pathway reduced sCAF accumulation and restored chemotherapy sensitivity, indicating that targeting this axis could significantly improve treatment efficacy in CRC.