Together, these results motivate combination strategies in MSS/TP53-mutated CRC aimed at converting “cold” tumors into “hot” ones—boosting antigenicity with DNA-damage-inducing chemotherapy or radiotherapy, restoring trafficking and function via vascular and stromal remodeling with anti-VEGF or TGF-β-pathway modulation, and addressing non-redundant inhibitory axes with dual-checkpoint approaches [25]. Here, TP53 is linked to colorectal carcinoma.