Fig. 6. The dense network and multiple regulatory immune responses in the TME.

A Capacity for intercellular communication between malignant cells and immune cells. Each line color indicates the ligands expressed by the cell population represented in the same color (labeled). The lines connect to the cell types that express the cognate receptors. The line thickness is proportional to the number of ligands when cognate receptors are present in the recipient cell type. The loops indicate autocrine circuits. The map quantifies potential communication but does not account for the anatomical locations or boundaries of the cell types. B Detailed view of the ligands expressed by each major cell type and the cells expressing the cognate receptors primed to receive the signal. Numbers indicate the quantity of ligand–receptor pairs for each intercellular link. Overview of selected ligand–receptor interactions of type 5 ductal cells under inhibitory interaction (C), stimulatory interaction (D), chemokines interaction (E), Th1-mediated interaction (F), and Th17-mediated interaction (G). P values are indicated by circle size, with the scale to the right (permutation test). The means of the average expression levels of interacting molecule 1 in cluster 1 and interacting molecule 2 in cluster 2 are indicated by color. Assays were carried out at the mRNA level but were used to extrapolate protein interactions.