Macrophages interacted with nearly all immune cell types specifically exhausted CD8+ T cells (CD8+ Tex) CD8+ Teff, CD4+ Treg 1 and Th17 by SPP1–CD44 interaction (Figure 4D), which only occurred in tumour sites, and no expression of SPP1 in macrophages from normal bowel tissue and adenoma was observed (Figure 4E). Here, CD44 is linked to adenoma.