SPP1 and cancer: Moreover, we identified several macrophage subtypes, including M2 polarization-related Spp1+ TAMs, which exhibit protumor characteristics and negative prognostic value for cancer treatment, including immunotherapy.32,51,54 Notably, microbiota-induced reprogramming from Spp1+ TAM to antigen-presenting Cd74+ TAM was observed, particularly with the synergistic effect of ICI treatment.