SPP1 and neoplasm: Given the role of SPP1+ TAMs in tumor malignancy, progression and prognosis highlighted in previous studies,32,52–54 we explored their role in ICI treatment in the context of gut microbiota using Spp1flox/floxLyz2-Cre+ conditional knockout mice (referred to as Spp1-cKO), in which Spp1 is specifically deleted in myeloid cells (e.g., macrophages) (Supplementary Fig. 9a).