Targeting microRNAs as key modulators of tumor immune response

Abstract

The role of immune response is emerging as a key factor in the complex multistep process of cancer. Tumor microenvironment contains different types of immune cells, which contribute to regulate the fine balance between anti and protumor signals. In this context, mechanisms of crosstalk between cancer and immune cells remain to be extensively elucidated. Interestingly, microRNAs (miRNAs) have been demonstrated to function as crucial regulators of immune response in both physiological and pathological conditions. Specifically, different miRNAs have been reported to have a role in controlling the development and the functions of tumor-associated immune cells. This review aims to describe the most important miRNAs acting as critical modulators of immune response in the context of different solid tumors. In particular, we discuss recent studies that have demonstrated the existence of miRNA-mediated mechanisms regulating the recruitment and the activation status of specific tumor-associated immune cells in the tumor microenvironment. Moreover, various miRNAs have been found to target key cancer-related immune pathways, which concur to mediate the secretion of immunosuppressive or immunostimulating factors by cancer or immune cells. Modalities of miRNA exchange and miRNA-based delivery strategies are also discussed. Based on these findings, the modulation of individual or multiple miRNAs has the potential to enhance or inhibit specific immune subpopulations supporting antitumor immune responses, thus contributing to negatively affect tumorigenesis. New miRNA-based strategies can be developed for more effective immunotherapeutic interventions in cancer.

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…[146][147] There is emerging evidence that miRNAs could serve as cancer immunotherapy and could serve as therapeutic targets in TB. [148][149] Cytokines and proteases TNF-α is essential to granuloma integrity, macrophage antimicrobial activity and ROSmediated Mtb killing. 150 TNF-α can however, also trigger cell necrosis and exacerbate inflammation, thereby aggravating TB pathology.…”

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Still, many questions remain to be addressed on immunotherapy, regarding the optimal schedule of treatment, identifying proper predictive biomarkers and co-targeting of the other key modulators of tumour immune response [10]. Recently, various miRNAs have been found to target key cancer-related immune pathways, which seem involved in the secretion of immunosuppressive or immunostimulating factors by cancer or immune cells [11].…”

MicroRNA-155-5p in pathogenesis of cancer

“…На сегодняшний день очевидно, что miR-155-5p играет существенную роль в патогенезе воспалитель-ных, иммунологических реакций, онкологических, кардиоваскулярных и некоторых инфекционных за-болеваний, а также манифестации синдрома Дауна и некоторых метаболических синдромов [10][11][12].…”

“…Одним из мощных факторов развития неоплазии являются нарушения функционирования иммунной системы, которые также сопровождаются либо пони-женной, либо повышенной экспрессией miR-155 [8,[10][11][12]21]. Иногда ее позиционируют в качестве од-ного из основных регуляторов иммунитета [22], что, на наш взгляд, несколько преувеличено.…”

“…Действие miR-155 в угнетении иммунитета в боль-шой степени зависит от ее связывания с транскрипта-ми генов, обеспечивающих функционирование TLR (toll-like receptor), липополисахаридов, интерлейкинов и интерферонов, а также генов, кодирующих анти-воспалительные факторы, в частности SOCS и SHIP (SH2-domain containing inositol-50-phosphatase, SH2-домен содержащая инозитол-5'-фосфатаза 1) [10,12]. Сигнальный путь JAK / STAT / SOCS (Janus kinase / signal transducer and activator of transcription / suppressor of cytokine signaling) во многом опреде-ляет функционирование иммунных клеток [26].…”