Fig. 7. Molecular interactions between tumor and immune compartment inferred by ligand-receptor co-expression.

a tSNE plot of 1620 B cells colored by cluster (left) or the origin (right). b Feature plot showing expression of follicular B-cell marker genes MS4A1 and CXCR5. c Feature plot showing expression of plasma B-cell marker genes. d tSNE plot of dendritic cells from AML tumors which are colored by cluster. e High expression of MKI67 in proliferating dendritic cells. f High expression of TIM3 (HAVCR2) in proliferating dendritic cells. g Circos-plot showing ligand-receptor pairs identified across pairs of cell types (cutoff value for interaction is 1). Red lines indicate pairs only identified in SLS-dominant tumors; green lines indicate pairs only identified in IS-dominant tumors. h Schematic showing the main discoveries from this study: identification of two cell states (SLS and IS), their differential cellular ecosystem with active crosstalk between tumor cells and microenvironment, and association with rapamycin resistance and immune modulation. In SLS tumor cells, upregulated APOE may modulate tumor-associated macrophages toward an immune-suppressive state by directly binding to TREM2/TYROBP receptor complex, leading to T-cell dysfunction and diminished T-cell clonal expansion; upregulated MDK expression may induce angiogenesis and drive persistence in response to mTORC1 inhibition. MDK is identified as a potential therapeutic target combined with rapamycin for persisting SLS tumor. In contrast, IS tumors with upregulated inflammatory pathways exhibit higher T-cell cytotoxicity/proliferation and sensitivity to rapamycin treatment. Figure is created with BioRender.com.