CD4 and neoplasm: 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).