Two independent studies revealed actionable mechanisms driving colorectal cancer immune escape and progression. A Cell Research report described an engineered 11–amino–acid peptide derived from APC C‑terminus that targets PTPN13, reversing immune-evasion pathways in colorectal tumors. The peptide restored immune recognition in preclinical models and represents a short-peptide therapeutic strategy against tumor phosphatase-mediated suppression. Complementing that, a multi-omics analysis highlighted dipalmitoylphosphatidylcholine (DPPC) as a lipid species that promotes colorectal tumor growth and remodels the immune microenvironment. The DPPC study used machine learning and omics integration to link metabolic remodeling with immune suppression, suggesting metabolic-lipid targets for combination therapy. Together these papers provide parallel, targetable routes—protein–protein interaction blockade and lipid metabolism modulation—to counteract immune escape in colorectal cancer, widening potential therapeutic strategies beyond established immunotherapy targets.