Moreover, mIHC staining confirmed different expression levels of CD68+ &APOE+ macrophages, FOXP3+ &TNFRSF4+ Tregs, VEGFA, and TGFβ signaling between the tumor microenvironment of the de novo mild OLK and the OLK with moderate to severe dysplasia in clinical study (Fig. 7a, b). The gene discussed is APOE; the disease is neoplasm.