Understanding cell‐cell communication and signaling in the colorectal cancer microenvironment

Abstract

Carcinomas are complex heterocellular systems containing epithelial cancer cells, stromal fibroblasts, and multiple immune cell‐types. Cell‐cell communication between these tumor microenvironments (TME) and cells drives cancer progression and influences response to existing therapies. In order to provide better treatments for patients, we must understand how various cell‐types collaborate within the TME to drive cancer and consider the multiple signals present between and within different cancer types. To investigate how tissues function, we need a model to measure both how signals are transferred between cells and how that information is processed within cells. The interplay of collaboration between different cell‐types requires cell‐cell communication. This article aims to review the current in vitro and in vivo mono‐cellular and multi‐cellular cultures models of colorectal cancer (CRC), and to explore how they can be used for single‐cell multi‐omics approaches for isolating multiple types of molecules from a single‐cell required for cell‐cell communication to distinguish cancer cells from normal cells. Integrating the existing single‐cell signaling measurements and models, and through understanding the cell identity and how different cell types communicate, will help predict drug sensitivities in tumor cells and between‐ and within‐patients responses.

Organoids and Colorectal Cancer

“…Importantly, a main limitation of ASC-PDOs is that the structures are made exclusively of epithelial cells and lack the stroma: fibroblasts, immune cells, nerves and vessels. The stroma or tumor microenvironment (TME) is largely responsible for tumor heterogeneity and plasticity and may contribute to CRC progression by means of reciprocal interactions with carcinoma cells [ 147 ]. Now, heterotypic structures that are more complex than PDOs rely on the transient co-culture of PDOs with stromal cell types that increase cell−cell interactions, or the use of short-lived tissue or tumor explants, which cannot be considered PDOs [ 148 , 149 , 150 ].…”

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

“…In the acute stage of pneumonia, the interaction between immune cells and other types of cells in tissue plays a key role in the development of the disease (Figure 10A ), as the cell–cell communication was suggested to be one of the critical approaches to translate the signals into the tissue and to maintain microenvironmental haemostasis. 27 , 28 TCs are new type of interstitial cells and their intercellular communication plays important roles in acute lung injury. 28 , 29 The protocol of co‐culture between PBICs from patients with acute pneumonia and primary TCs from lung sections is shown in Figure S5 .…”

“…27,28 TCs are new type of interstitial cells and their intercellular communication plays important roles in acute lung injury. 28,29 The protocol of co-culture between PBICs from patients with acute pneumonia and primary TCs from lung sections is shown in Figure S5. Alteration of immune cell F I G U R E 7 T-cell immune patterns across healthy volunteers and patients with acute asthma and stable asthma.…”

Clinical challenges of tissue preparation for spatial transcriptome

“…The cell–cell communication controls the signalling and function between cells and maintains microenvironment homeostasis, including initiator cells, signal network factors, communicating conditions and receptor cells 39 . Within tumour microenvironments, the cell–cell communication and interaction can control the microenvironmental ecology, regulate cancer cell growth and sensitivity to drugs and dominate the formation of inter‐cellular heterogeneity 40 . The spatial cell–cell communication positions the interactions among cancer cells, immune cells, resident cells and endothelial cells; the activations of inflammatory mediators and the remodelling of localised metabolism.…”