(A) Berlin et al. developed the APTKA organoid CRC model. Notably, the multivisceral landscape of CRC metastasis driven by the APTKA organoid model mimics human stage IV CRC. (B) Single-cell deconvolution of the CRC metastatic sites identified CSCs as important regulators of PC. CAFs interact with CSC via important CSC-inducing pathways. Next, an immunosuppressive TME becomes generated by the presence of exhausted CD8⁺ T cells, immunosuppressive Th1 CD4⁺ cells, and B cells with loss of antigen-presentation machinery. In contrast, NK cells activate and shift their metabolic status toward OXPHOS. (C) Mice with APTKA PC CRC responded to a PC-specific therapeutic approach. The findings suggest treatment of anti-PD1 biologicals by intraperitoneal application may reactivate exhausted CD8⁺ T cells and increase tumor cell death of intraperitoneal CRC in patients.