Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Abstract

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

Immunogenic Cell Death-Relevant Damage-Associated Molecular Patterns and Sensing Receptors in Triple-Negative Breast Cancer Molecular Subtypes and Implications for Immunotherapy

“…It is becoming increasingly clear that DAMPs show robust adjuvanticity during ICD procedures ( 35 ), thus enhancing the antitumor immune effect of ICIs therapy ( 36 ). Therefore, we propose here to identify ICD-activating or ICD-suppressive DAMPs subtypes or hallmarks to explore the potential role of a combined DAMPs and immune status classifier for TNBC.…”

Cardiac Remodeling After Myocardial Infarction: Functional Contribution of microRNAs to Inflammation and Fibrosis

“…In recent years, miRNA-targeted therapeutics have been tested in clinical trials, mostly in cancer; because of the limited space allowed in this minireview, for these aspects we refer to dedicated reviews ( 101 – 104 ). A successful example of how to develop a miRNA-based therapy in cardiovascular medicine is given by miR-132, which has among its targets FOXO3 and SERCA2a ( 49 , 105 ).…”

Editorial on Special Issue “Immunotherapy, Tumor Microenvironment and Survival Signaling”

“…Another review focuses on the role of microRNA in the modulation of damage-associated molecular patterns (DAMP) [ 16 ]. Immunogenic cell death (ICD) which is triggered by several ICD-inducers released into tumor microenvironment plays a major role in stimulating anti-tumor response [ 16 ]. The exposure of DAMP such as calreticulin, ATP, Hsps and HMGB1 confers adjuvanticity to cancer cell death [ 16 ].…”

“…Immunogenic cell death (ICD) which is triggered by several ICD-inducers released into tumor microenvironment plays a major role in stimulating anti-tumor response [ 16 ]. The exposure of DAMP such as calreticulin, ATP, Hsps and HMGB1 confers adjuvanticity to cancer cell death [ 16 ]. The authors review the main microRNA that target DAMPs such as Hsp 70, Hsp 90, HMGB1, calreticulin [ 16 ].…”

“…The exposure of DAMP such as calreticulin, ATP, Hsps and HMGB1 confers adjuvanticity to cancer cell death [ 16 ]. The authors review the main microRNA that target DAMPs such as Hsp 70, Hsp 90, HMGB1, calreticulin [ 16 ].…”