miR-155 aberrant expression impairs tumor rejection because of its targeting of ICOSL and multiple pathways implicated in the antitumor response.

Cancer treatments have dramatically improved because of advances in surgery, radiotherapy, and chemotherapy. Although the duration of remission has steadily increased in recent years, preventing metastasis and achieving complete remission is still beyond reach for various types of cancers. However, recent advancements in immunology have facilitated the development of immunotherapies aimed at enhancing the specificity and efficacy of natural anticancer immune responses while impairing the inhibitory effects of immune checkpoints. Although immunotherapies combined with other treatment modalities have already produced remarkable results in previously untreatable tumors, many patients still do not achieve complete remission. In this review, we explore the effects of miR-155, a microRNA that plays a critical role in initiation and resolution of both innate and adaptive immunity. Among the many target transcripts of miR-155 are those encoding immune checkpoints, cell cycle regulators, epigenetics regulators, transcription factors, DNA repairs factors, and factors involved in various signaling pathways. The inhibitory effects of miR-155 on its target transcripts are likely to be context- and dose-dependent. As certain miR-155 targets can have opposing effects based on their dose and activity, therapies aimed at increasing or decreasing miR-155 levels can potentially backfire, inhibiting the beneficial effects of widely used anticancer drugs. Precise monitoring and adjustment of miR-155 levels, depending on the type and stage of tumors, should enhance the effectiveness of immunotherapies and increase the percentage of patients achieving complete remission in the future, particularly when immunotherapies are combined with chemotherapies. SIGNIFICANCE STATEMENT: Although immunotherapies developed the last decade have brought hope and improved cancer treatments, prevented metastasis, and increased the rate of complete remission, many aspects of the anticancer immune response are controlled by miR-155, a microRNA whose activity is both context- and dose-dependent. Therefore, it is essential to determine the optimal levels of miR-155 activity according to the type and stage of tumors, in order to fully unlock the potential of immunotherapies in combination with surgery, radiotherapies, or chemotherapies.