Towards A More Faithful Ex Vivo Modelling Of Tumor-Immune-Stroma Communication

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About this Research Topic

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Background

Tumors seldom grow in isolation, they are in constant communication with surrounding stromal cells, vasculature, immune cells, and other tissue components such as adipose tissue and neuronal networks. Tumor cells also interact and utilize acellular components such as ECM proteins constructed by fibroblasts or macrophages. These interactions have tremendous impact on the fitness, differentiation, and migration of tumors, and are a major area of clinical research and pharmacological targeting. These efforts have resulted in the development of stroma-targeted drugs such as antiangiogenic and antifibrotic agents, and notably led to the emergence of immunotherapies. The complexity of tumor microenvironments, beyond tumor cell heterogeneity, has gained more appreciation in the last decade. This knowledge has accelerated efforts to model the heterogeneity of interactions involving host stroma or immune cells within a growing tumor, while recapitulating the niche and architecture of the organ or host site.

Currently, the field of cancer immunology relies heavily on utilizing mouse xenograft or syngeneic models for gaining biological insights and for developing new biomarkers or therapeutics. While mouse models recapitulate several key aspects of tumor–microenvironment interactions, they are not suitable for capturing the inter– and intra–patient tumor heterogeneity, nor do they scale well for large–scale screening efforts. Patient surgery/biopsy samples have emerged as a powerful alternative in this arena, but they are limited in utility due to short survival windows and stark differences in immune cell composition. There is now active interest in developing better ex vivo models of cancer-immune and cancer-stroma interactions that are feasible, tractable, and scalable. Advances in microfluidics, micropatterning, and 3D architecture have enabled longer-term culture of human or mouse tumors with higher fidelity to actual biology.

This Research Topic will highlight work that advances current modeling of the context-dependent interaction between tumors and microenvironmental components (including but not limited to immune cells, stromal fibroblasts, vasculature, or neurons). In doing so, such work can help identify potential prognostic markers as well as factors influencing the efficacy of immunotherapies or other tumor-targeted therapies.

We encourage the contribution of Original Research Articles, Reviews, Methods, Mini-Reviews, Perspectives and Opinions related to the following, but not limited to:
• 2–D and 3–D culture systems for modeling human/mouse/chimeric interactions in the tumor microenvironment
• Microfluidics-based systems and bioreactor assemblies for long-term culture of primary cells including stromal or immune cells
• Novel biomaterial and scaffolding technology for faithful mimicry of native tissue architecture
• Ex vivo culture conditions focused on specific aspect of tumor biology (e.g.- metastatic seeding, hypoxa stress, neuronal crosstalk)
• Drug or biomarker screen approaches with functional readouts, harnessing existing or newly-developed ex vivo culture systems

Please note: studies consisting solely of bioinformatic investigation of publicly available genomic/transcriptomic/proteomic data do not fall within the scope of the section unless they are expanded and provide significant biological or mechanistic insight into the process being studied.

We accept different article types including Mini-Reviews, Brief Research Reports and Perspectives. A full list of accepted article types, including descriptions, can be found at this link.

Research Topic Research topic image

Keywords: ex vivo, organoid, spheroid, in vitro, 3D, microfluidics, micropatterning, bioreactor, macrophages, fibroblasts, vasculature, screen, perturbation

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