title: Noncoding RNAs and immune checkpoints-clinical implications as cancer therapeutics.
abstract: A major mechanism of tumor development and progression is silencing of the patient's immune response to cancer-specific antigens. Defects in the so-called cancer immunity cycle may occur at any stage of tumor development. Within the tumor microenvironment, aberrant expression of immune checkpoint molecules with activating or inhibitory effects on T lymphocytes induces immune tolerance and cellular immune escape. Targeting immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and its ligand PD-L1 with specific antibodies has proven to be a major advance in the treatment of several types of cancer. Another way to therapeutically influence the tumor microenvironment is by modulating the levels of microRNAs (miRNAs), small noncoding RNAs that shuttle bidirectionally between malignant and tumor microenvironmental cells. These small RNA transcripts have two features: (a) their expression is quite specific to distinct tumors, and (b) they are involved in early regulation of immune responses. Consequently, miRNAs may be ideal molecules for use in cancer therapy. Many miRNAs are aberrantly expressed in human cancer cells, opening new opportunities for cancer therapy, but the exact functions of these miRNAs and their interactions with immune checkpoint molecules have yet to be investigated. This review summarizes recently reported findings about miRNAs as modulators of immune checkpoint molecules and their potential application as cancer therapeutics in clinical practice.
authors.affiliation: Division of Clinical Oncology, Internal Medicine, Medical University of Graz, Graz, Austria.|Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.|Center for Biomarker Research in Medicine, Graz, Austria.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Smolle
authors.affiliation: University of Pennsylvania, Philadelphia, USA.
authors.forename: Horatiu N
authors.initials: HN
authors.lastname: Calin
authors.affiliation: Division of Clinical Oncology, Internal Medicine, Medical University of Graz, Graz, Austria.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.|Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D016207:Cytokines; D035683:MicroRNAs; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D022661:RNA, Untranslated
keywords: CTLA4; PD1; PDL1; cancer; immune checkpoints; miRNA; therapy