SPP1 macrophages and CAFs co‐localise around tumours in ICB non‐responders to form a tumour immune barrier. Blockade of SPP1 or macrophage‐specific deletion of Spp1 resulted in enhanced efficacy of anti‐PD‐1 therapy in a mouse model of hepatocellular carcinoma, accompanied by a reduced proportion of CAF infiltration and an increased proportion of cytotoxic T‐cell infiltration. The gene discussed is SPP1; the disease is neoplasm.