Like cluster 3, TAMs in cluster 4 upregulate TREM2, however in contrast, they also upregulate APOE, a fatty acid metabolism gene studied extensively in neurological disorders72 and recently associated with macrophage subsets in breast cancer42, as well as APOC1, which has been shown as a potential prognostic biomarker for lung cancer progression73 and when inhibited, promotes transformation of M2 polarized TAMs to an M1 state and enhances anti-PD1 immunotherapy in hepatocellular carcinoma74. The gene discussed is TREM2; the disease is lung carcinoma.