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Fig. 4 | Military Medical Research

Fig. 4

From: Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

Fig. 4

Cell communication between various cells in the tumour immune microenvironment. a Principles of analytical tools for investigating ligand-receptor interactions based on scRNA-seq data. These tools take advantage of databases of known ligand-receptor pair interactions. Some tools also consider the alterations in downstream pathways in receiver cells. b Malignant cells closely interact with immune cells. Tumour-associated macrophages (TAMs) were found to interact with malignant cells via the epidermal growth factor receptor (EGFR)-amphiregulin (AREG) ligand-receptor pair. oncostatin M (OSM) derived from TAMs also interacts with its receptor on malignant cells. T cells and malignant cells interact through T cell immunoreceptor with Ig and ITIM domains (TIGIT)-PVR and hepatitis A virus cellular receptor 2 (HAVCR2)-galectin 9 (LGALS9). CAFs and malignant cells interact through interlukin (IL)-6-IL6R, integrin receptor interactions with collagen and fibronectin, thrombospondin 1 (THBS1) ligands, and leucine rich repeat containing G protein-coupled receptor 4 (LGR4)-R-spondin 3 (RSPO3). Interactions between immune cells in the TIME have also been demonstrated. Cancer-associated fibroblasts (CAFs) recruit Tregs by secreting C-X-C motif chemokine ligand 12 (CXCL12) and are also correlated with M2 macrophages via periostin. TAMs show decreased CXCL12- C-X-C motif chemokine receptor 3 (CXCR3) and CXCL12- C-X-C motif chemokine receptor 4 (CXCR4) interactions and enhanced CD86-CTLA-4 and programmed death-ligand 1 (PD-L1)-programmed death-1 (PD-1) interactions with T cells. TAMs also secrete CXCL10, CCL22, and CCL5 to recruit T cells. TAMs and CAFs interact through C3a and C3aR. Therapeutic interventions, such as perturbation of complement C3a (C3a) and complement C3a receptor (C3aR), antibodies targeting triggering receptor expressed on myeloid cells 2 (TREM2), and IL-17 blockade, have displayed promising outcomes. TAMs tumour-associated macrophages, EGFR epidermal growth factor receptor, AREG amphiregulin, OSM oncostatin M, TIGIT T cell immunoreceptor with Ig and ITIM domains, HAVCR2 hepatitis A virus cellular receptor 2, LGALS9 galectin 9, IL interlukin, THBS1 thrombospondin 1, LGR4 leucine rich repeat containing G protein-coupled receptor 4, RSPO3 R-spondin 3, CAFs cancer-associated fibroblasts, CXCL C-X-C motif chemokine ligand, CXCR C-X-C motif chemokine receptor, PD-L1 programmed death-ligand 1, PD-1 programmed death-1, C3a complement C3a, C3aR complement C3a receptor, ECM extracellular matrix, TREM2 triggering receptor expressed on myeloid cells 2, CCL C–C motif chemokine ligand

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