SPP1, also known as osteopontin, is upregulated in various cancers and involved in various biological processes, such as inflammation, fibrosis, cancer progression, and metastasis.25 Our result indicated that macrophages were the main source of SPP1 and various kinds of immune cells, including B cells, CD4 + T cells, CD8 + T cells, mast cells, and neutrophils, could serve as the receiver or the influencer of SPP1 (Fig. 11c, d and Supplementary Fig. S14a). Here, CD4 is linked to cancer.