Role of miRNAs in immune responses and immunotherapy in cancer

Abstract

In the past decade, the study of mechanisms of cancer immunity has seen a prominent boom, which paralleled the increased amount of research on the clinical efficacy of immune checkpoint blockade in several lethal types of cancers. This conspicuous effort has led to the development of successful immunotherapy treatment strategies, whose medical impact has been recognized by the awarding of 2018 Nobel Prize in Physiology or Medicine to the two pioneers of check point inhibitor research, Tasuku Honjo and James Allison. Despite these promising achievements, the differences in the clinical response rate in different cancer patients and the high risk of toxicity of immune‐based therapies represent crucial challenges. More remarkably, the causes responsible for different outcome (success vs failure) in patients with tumor having same histotype and clinical characteristics remain mostly unknown. MicroRNAs (miRNAs), small regulatory noncoding RNA molecules representing the most studied component of the dark matter of the human genome, are involved in the regulation of many pathways of cancer and immune cells. Therefore, understanding the role of miRNAs in controlling cancer immunity is necessary, as it can contribute to reveal mechanisms that can be modulated to improve the success of immunetherapy in cancer patients. Here, we discuss the latest findings on immune pathways regulated by miRNAs in cancer, miRNA‐mediated regulation of immune cells in the tumor microenvironment, and miRNAs as potential target for immunotherapies.

MiRNA expression patterns are associated with tumor mutational burden in lung adenocarcinoma

“…TMB has emerged as an independent biomarker to predict patient responses to treatment with ICIs, 18,19,49,50 and the negative predictive role of low TMB could not be overcome by the combination immunotherapy. 50 Several studies have shown to effectively measure TMB from liquid biopsies/blood, [51][52][53][54] this might be an alternative to the biopsies since it is less invasive and easily repeatable. However, TMB assessment by liquid biopsy must face the problem that the circulating DNA deriving from tumor cells is often only a small fraction of the circulating cell free DNA and it needs further investigation and may be clarified within the ongoing clinical trials.…”

Peer Review #2 of "Comprehensive analysis of an lncRNA-miRNA-mRNA competing endogenous RNA network in pulpitis (v0.1)"

“…Immune response can be triggered by inflammatory mediators or cytokines produced by infectious cells through the transcriptional or post-transcriptional regulations. The expression of ncRNAs may be closely related to the development of immune cells (particularly monocytes, macrophages, NK cells, T helper cells, CD8 + T cells, and Treg cells) and the maintenance of immune system homeostasis (Cortez et al, 2019;Imamura & Akimitsu, 2014). For instance, lincRNA-Cox2 regulates the release of inflammatory mediators and cytokines by stimulation of TLR2 in bacterial infections (Carpenter et al 2013), and miR-155 exerts an antiproliferative effect on CD8 + T cells in response to the type I interferon signaling (Gracias et al, 2013).…”

The functions and targets of miR‐212 as a potential biomarker of cancer diagnosis and therapy

“…miRNAs participate in both innate and adaptive immunity by interacting with various immune cells, including monocytes, macrophages, NK cells and T helper cells, in differentiation, activation and other functions. The relationship between miRNAs and immunity has important effects on cancer progression …”

“…The relationship between miRNAs and immunity has important effects on cancer progression. 44 An earlier study on the biological functions of miRNA-212 found it to interact with the neurons as well as inflammation. 11 Studies performed recently demonstrated that miRNA-212-3p can interact with immune cells and inflammatory cytokines in the occurrence or development of cancer.…”