Non-coding RNAs in the tumoral microenvironment: mechanisms, regulatory networks and clinical applications in cancer immunity

Despite the efforts of the scientific community, cancer is still a leading cause of death worldwide. Immunotherapy, a ground-breaking strategy for cancer treatment, holds an extraordinary potential also for the most refractory tumors, but toxicity, poor response or cancer relapse still limits its application.
A still mysterious crosstalk exists between immune and cancer cells, whose interaction and molecular mechanisms define the dual nature of the immune cells in the tumour microenvironment (TME), which can have both pro and antitumorigenic functions. A novel concept is recently emerging: the regulation of immune cells differentiation, activation and function in the TME is orchestrated by complex epigenetic and transcriptional changes, where not only transcription factors and soluble mediators play a critical role, but also non-coding RNAs (ncRNAs). Increasing evidence show that miRNAs, lncRNAs and circRNAs have a role in regulating the diverse stages of tumor immunity through modulation of the equilibrium between immune activation and immunosuppression.

This collection aims to explore the pivotal role of ncRNAs in the dynamics of the TME, highlighting how the different classes co-operate in antagonist/synergic fashion, exploring their role in cancer development, progression, and response to the immunotherapy. We seek contributions that provide novel insight on how ncRNAs regulate gene expression at post-transcriptional and epigenetic level, affect the communication between immune cells and cancer, and extracellular vesicles mediated interaction involving ncRNAs. At diagnostic level, for their potential as biomarkers of prognosis, we want to highlight how ncRNA signatures can predict the course of disease in immuno-oncology, in particular for liquid biopsy applications. In therapy, targeting of ncRNAs represents an attractive approach: up-regulation or silencing of ncRNAs can modulate specific signaling pathways, fine tuning the activity of the immune cells to maintain the balance between side-effects and cytotoxicity.

Functions and regulatory mechanisms:
Highlight the functions and regulatory mechanisms of non-coding RNAs (ncRNAs) and RNA-binding proteins (RNB proteins) in cancer immunity, in particular concerning CD4+/CD8+ cells, tumor-associated macrophages and NK cells.
• Dysregulated ncRNAs/RNB proteins in tumor immune escape mechanisms, cancer resistance to immunotherapy and relapse
• Non-coding RNAs governing tumor associated macrophages (TAMs) infiltration and the M1/M2 polarization
• Non-coding RNAs in secreted exosomes, mediating the communication between cancer and immune cells
• Mechanisms of blockade of antigen presentation mediated by ncRNAs
• Non-coding RNAs in CD8+ T cell exhaustion and senescence
• Regulation of inhibitory immune checkpoint-mediated immune evasion mediated by ncRNAs
• Epigenetic changes mediated by ncRNAs in cancer immunity
• Characterization of the molecular mechanisms implicated in the crosstalk.

Non-coding RNA-based anticancer immunotherapy
ncRNAs are involved in mediating the communication between cancer cells and immune cells and represent crucial resistance mechanisms that can abrogate the effect of immunotherapy. Highlight the clinical applications concerning:
• Use of ncRNAs profiling/RNB proteins expression as predictive biomarkers of response to immunotherapy
• RNA-based therapeutics such as: antisense oligonucleotides, small interfering RNAs or anti-miRNA: specificity, delivery and tolerability
• Targeting non-coding RNAs in immunosuppressive cells (such as myeloid-derived suppressive cells-MDSCs and tumor-associated macrophages-TAMs) to overcome cancer therapy resistance


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• Brief Research Report
• Editorial
• FAIR² Data
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• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: crispr cas9, non coding RNAs, RNB proteins, tumoral microenvironment, Cancer immunotherapy, therapy resistance, tumor microenvironment (TME), immune microenvironment (TIME), immune cells, stroma cells, response immune, immune escape, epigenome, ncRNA, miRNAs, lncRNAs, circRNAs and piRNAs

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.