M2 macrophages increase organoid viability and reduce sensitivity to paclitaxel in co-culture. The M2 repolarizer, BMS777607, reduced organoid viability in a macrophage-dependent manner. In a platinum-sensitive huPDX model, the TAM-targeted CSF-1R inhibitor, BLZ945, combined with paclitaxel reduced tumor burden with no regrowth, reversing resistance observed with paclitaxel alone. Here, CSF1R is linked to neoplasm.