Cancers develop within a complex tissue environment characterized by a dynamic communication between cancer cells, immune and stromal cells during all stages of carcinogenesis. Within the tumor microenvironment (TME), the extracellular matrix (ECM) provides a scaffold for the organization of cancer cells and spatial cues that control their ability for survival, growth, differentiation, and migration. In turn, cancer and stromal cells release soluble factors (cytokines, growth factors, exosomes) remodeling the ECM stiffness, thus driving stromal hardening and fibrosis.
A fibrotic TME results from the interplay between a variety of cell types composing the “normal compartment” of the tumor mass (mainly fibroblasts, endothelial cells, inflammatory, and immune cells), tumor cells, and the bi-directional interaction with the ECM. Chronic pro-inflammatory stimuli and altered immune infiltration govern tumor fibrosis. Many of the TME cells (macrophages, neutrophils, and fibroblasts) are endowed with elevated cellular and metabolic plasticity, phenomena cooperating in the process of immune cell polarization. Immunosuppressive and immunometabolic TME stimuli can ‘re-educate’ immune cells to acquire pro-tumor activities that synergize by stimulating tumor cell proliferation, survival, migration, and invasion. Accordingly, depending on the different TME stimuli, also fibrosis may act as tumor-promoting or tumor-suppressing factor. Thus, also the dual role of fibrosis in cancer evolves during the continuum of cancer growth. Of notice, exacerbated fibrosis has been observed as a key feature of different tumors, such as pancreatic, liver, and lung cancers.
The precise role of the TME components and the molecular mechanisms governing their dynamic interactions in fibrotic tumors are still not completely defined, even if several cellular and molecular mechanisms have been proposed and investigated.
Within this Research Topic, we aim to collect Original Research, Review, Mini-review, and Perspective articles reviewing/discussing the state and/or proposing novel insights in basic and translational research linking fibrosis and cancer progression. Areas of interest will include but will not be limited to:
• High-throughput (“omics”) approaches followed by experimental validation to dissect molecular mechanisms linking fibrosis with cancer progression via microenvironmental cues
• Fibrosis-oriented molecular and cellular mechanisms supporting tumor progression and the generation of a metastasis permissive soil
• The role of chronic inflammation in the fibrotic process and the contribution in the generation of the pre-metastatic niche
• Metabolic and immunometabolic reprogramming as drivers of fibrosis
• Fibrosis-mediated metabolic reprogramming supporting tumor progression and immune cell exhaustion/anergy
• Preclinical and/or clinical studies targeting fibrosis as a relevant hallmark to be targeted in next-generation immunotherapy approaches
• Novel diagnostic or prognostic tools for cancer fibrosis detection and tracing (molecular imaging, circulating biomarkers including proteomics, metabolomics), in cancer progression.
• In vivo (animal models) in vitro (organoids, tissue culture) models to dissect the relationship between inflammation, fibrosis, and cancer for pharmacological research, and drug discovery.
Cancers develop within a complex tissue environment characterized by a dynamic communication between cancer cells, immune and stromal cells during all stages of carcinogenesis. Within the tumor microenvironment (TME), the extracellular matrix (ECM) provides a scaffold for the organization of cancer cells and spatial cues that control their ability for survival, growth, differentiation, and migration. In turn, cancer and stromal cells release soluble factors (cytokines, growth factors, exosomes) remodeling the ECM stiffness, thus driving stromal hardening and fibrosis.
A fibrotic TME results from the interplay between a variety of cell types composing the “normal compartment” of the tumor mass (mainly fibroblasts, endothelial cells, inflammatory, and immune cells), tumor cells, and the bi-directional interaction with the ECM. Chronic pro-inflammatory stimuli and altered immune infiltration govern tumor fibrosis. Many of the TME cells (macrophages, neutrophils, and fibroblasts) are endowed with elevated cellular and metabolic plasticity, phenomena cooperating in the process of immune cell polarization. Immunosuppressive and immunometabolic TME stimuli can ‘re-educate’ immune cells to acquire pro-tumor activities that synergize by stimulating tumor cell proliferation, survival, migration, and invasion. Accordingly, depending on the different TME stimuli, also fibrosis may act as tumor-promoting or tumor-suppressing factor. Thus, also the dual role of fibrosis in cancer evolves during the continuum of cancer growth. Of notice, exacerbated fibrosis has been observed as a key feature of different tumors, such as pancreatic, liver, and lung cancers.
The precise role of the TME components and the molecular mechanisms governing their dynamic interactions in fibrotic tumors are still not completely defined, even if several cellular and molecular mechanisms have been proposed and investigated.
Within this Research Topic, we aim to collect Original Research, Review, Mini-review, and Perspective articles reviewing/discussing the state and/or proposing novel insights in basic and translational research linking fibrosis and cancer progression. Areas of interest will include but will not be limited to:
• High-throughput (“omics”) approaches followed by experimental validation to dissect molecular mechanisms linking fibrosis with cancer progression via microenvironmental cues
• Fibrosis-oriented molecular and cellular mechanisms supporting tumor progression and the generation of a metastasis permissive soil
• The role of chronic inflammation in the fibrotic process and the contribution in the generation of the pre-metastatic niche
• Metabolic and immunometabolic reprogramming as drivers of fibrosis
• Fibrosis-mediated metabolic reprogramming supporting tumor progression and immune cell exhaustion/anergy
• Preclinical and/or clinical studies targeting fibrosis as a relevant hallmark to be targeted in next-generation immunotherapy approaches
• Novel diagnostic or prognostic tools for cancer fibrosis detection and tracing (molecular imaging, circulating biomarkers including proteomics, metabolomics), in cancer progression.
• In vivo (animal models) in vitro (organoids, tissue culture) models to dissect the relationship between inflammation, fibrosis, and cancer for pharmacological research, and drug discovery.
