Using the TME-free tumoroid cultures, we were able to directly test how CRC tumoroids influence macrophage polarization, revealing a strong induction of the SPP1+ state in human macrophages derived from circulating monocytes, indicating that carcinoma cells themselves can induce this state in the absence of cancer-associated fibroblasts (CAFs) or a hypoxic environment. Here, SPP1 is linked to carcinoma.