RESUMO
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.
Assuntos
Inflamação/imunologia , Células Supressoras Mieloides/imunologia , Neoplasias/imunologia , RNA Longo não Codificante/fisiologia , Animais , Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Linhagem da Célula , Epigênese Genética , Previsões , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia , Camundongos , Células Supressoras Mieloides/classificação , Neoplasias/genética , Neoplasias/terapia , Óxido Nítrico/metabolismo , Pseudogenes , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , RNA Neoplásico/imunologia , RNA Neoplásico/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Evasão Tumoral , Microambiente TumoralRESUMO
BACKGROUND: Immunotherapy is an effective method for preventing metastasis and recurrence of carcinoma. Hepatocellular carcinoma (HCC) is a common malignancy with a high rate of recurrence, and has not successfully been introduced to immunotherapy. METHODS: Peripheral blood mononuclear cells were isolated from whole blood of HCC patients and stimulated to transform into dendritic cells (DCs). These DCs were then transfected with RNA extracted from HepG-2 hepatoma cells to induce expression of specific antigens. RESULTS: The transfected DCs stimulated T lymphocytes to produce cytotoxic T lymphocytes, which specifically attacked HepG-2 cells. Injection of T lymphocytes from HCC patients and transfected DCs into severe combined immunodeficiency mice limited the growth of HepG-2 tumors. CONCLUSION: A specific immune response against hepatoma can be generated in vivo by administering DCs transfected with RNA from a specific tumor. This method may have therapeutic application in humans to reduce recurrence of HCC.
Assuntos
Vacinas Anticâncer/imunologia , Carcinoma Hepatocelular/imunologia , Células Dendríticas/transplante , Neoplasias Hepáticas/imunologia , RNA Neoplásico/imunologia , Animais , Antígenos de Neoplasias/imunologia , Células Dendríticas/imunologia , Citometria de Fluxo , Humanos , Técnicas In Vitro , Camundongos , Linfócitos T Citotóxicos/imunologia , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Subline B16-F10, a variant cell line of B16 melanoma, is highly metastatic to the lung when injected intravenously into C57BL/6 mice. This experimental metastasis model was used to test the anti-tumor effect of exogenous RNA extracted from the lymphoid organs of immunized animals with B16-F10 cells. This RNA preparation is referred to as B16-RNA. Adoptive immunotherapy with lymphocytes treated with B16-RNA was effective in reducing significantly the number of pulmonary metastatic nodules. Lymphocytes incubated with medium alone or with RNA from non-immunized animals (N-RNA) were used as controls. The ability of B16-RNA in modulating antimetastatic activity of normal lymphocytes is abolished by hydrolysis with KOH. This finding indicates that the integrity of the polynucleotide chain is essential for the activity of B16-RNA. The anti-tumor effect of lymphocytes treated with B16-RNA was enhanced by incubation with a low dose of interleukin-2 (IL-2). A possible role of the double-stranded RNA dependent protein kinase in this phenomenon is discussed.