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Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-beta production capable of improving dendritic cell function

(2013) EUROPEAN JOURNAL OF IMMUNOLOGY. 43(7). p.1849-1861
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Abstract
Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine-polycytidylic acid (poly I:C) and polyadenylic-polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN- autocrine loop, dsRNA-elicited IFN- production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN- at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN- produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN- production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3(-/-) mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1(-/-) mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN- production and contribute to the antitumoral response.
Keywords
IFN-beta, TLR3, dsRNA, Dendritic cells, Tumor immunity, TOLL-LIKE RECEPTOR-3, OPERABLE BREAST-CANCER, DOUBLE-STRANDED-RNA, I INTERFERON, TUMOR-CELLS, HEPATOCELLULAR-CARCINOMA, TRIGGERS APOPTOSIS, RANDOMIZED TRIAL, IMMUNE-RESPONSE, INNATE IMMUNITY

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Citation

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Chicago
Gatti, Gerardo, Nicolás Gonzalo Nuñez, David Andrés Nocera, Lien Dejager, Claude Libert, Constancio Giraudo, and Mariana Maccioni. 2013. “Direct Effect of dsRNA Mimetics on Cancer Cells Induces Endogenous IFN-beta Production Capable of Improving Dendritic Cell Function.” European Journal of Immunology 43 (7): 1849–1861.
APA
Gatti, G., Gonzalo Nuñez, N., Andrés Nocera, D., Dejager, L., Libert, C., Giraudo, C., & Maccioni, M. (2013). Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-beta production capable of improving dendritic cell function. EUROPEAN JOURNAL OF IMMUNOLOGY, 43(7), 1849–1861.
Vancouver
1.
Gatti G, Gonzalo Nuñez N, Andrés Nocera D, Dejager L, Libert C, Giraudo C, et al. Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-beta production capable of improving dendritic cell function. EUROPEAN JOURNAL OF IMMUNOLOGY. 2013;43(7):1849–61.
MLA
Gatti, Gerardo, Nicolás Gonzalo Nuñez, David Andrés Nocera, et al. “Direct Effect of dsRNA Mimetics on Cancer Cells Induces Endogenous IFN-beta Production Capable of Improving Dendritic Cell Function.” EUROPEAN JOURNAL OF IMMUNOLOGY 43.7 (2013): 1849–1861. Print.
@article{4217803,
  abstract     = {Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine-polycytidylic acid (poly I:C) and polyadenylic-polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN- autocrine loop, dsRNA-elicited IFN- production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN- at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN- produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN- production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3(-/-) mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1(-/-) mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN- production and contribute to the antitumoral response.},
  author       = {Gatti, Gerardo and Gonzalo Nuñez, Nicolás and Andrés Nocera, David and Dejager, Lien and Libert, Claude and Giraudo, Constancio and Maccioni, Mariana},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keywords     = {IFN-beta,TLR3,dsRNA,Dendritic cells,Tumor immunity,TOLL-LIKE RECEPTOR-3,OPERABLE BREAST-CANCER,DOUBLE-STRANDED-RNA,I INTERFERON,TUMOR-CELLS,HEPATOCELLULAR-CARCINOMA,TRIGGERS APOPTOSIS,RANDOMIZED TRIAL,IMMUNE-RESPONSE,INNATE IMMUNITY},
  language     = {eng},
  number       = {7},
  pages        = {1849--1861},
  title        = {Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-beta production capable of improving dendritic cell function},
  url          = {http://dx.doi.org/10.1002/eji.201242902},
  volume       = {43},
  year         = {2013},
}

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