Suppression of dendritic cell differentiation through cytokines released by Primary Effusion Lymphoma cells

Cirone, Mara; Lucania, Giuseppe; Aleandri, Silvia; Borgia, G.; Trivedi, Pankaj; Cuomo, Laura; Frati, Luigi; Faggioni, Alberto

doi:10.1016/j.imlet.2008.06.011

Cited by 41 publications

(40 citation statements)

References 24 publications

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“…These findings indicate that such combination could be exploited to improve the outcome of anti-cancer therapy against PEL. In a previous study we showed that AG490 induces an immunogenic cell death in PEL cells [9] and other authors have also reported that AG490 is able to counteract the cancer-mediated immune suppression, that correlates with STAT3 hyper-activation in dysfunctional DC cultured in the presence of tumor released factors [24,36] or present in the tumor environment [23]. Based on this knowledge, we suggest that AG490, especially if combined with autophagy inhibitors, could represent an ideal anticancer therapy against PEL as well as against other tumors characterized by the release of factors that activate STAT3 in an autocrine and paracrine fashion.…”

Section: Discussionmentioning

confidence: 86%

Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells

Granato¹,

Chiozzi²,

Filardi³

et al. 2015

Cancer Letters

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Section: Discussionmentioning

confidence: 86%

Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells

Granato¹,

Chiozzi²,

Filardi³

et al. 2015

Cancer Letters

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“…It is a critical component of the tumor microenvironment of KS and is present in high circulating levels in patients with PEL and MCD (8)(9)(10). It serves both as a key growth factor for infected cells (9,11) and, together with IL-10, assists in protection of PEL cells from immune eradication through the inhibition of dendritic cell maturation (12). IL-6 is also a proangiogenic factor and thus likely contributes to the vascularity of KS lesions via its induction of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) (13,14).…”

mentioning

confidence: 99%

An RNA Element in Human Interleukin 6 Confers Escape from Degradation by the Gammaherpesvirus SOX Protein

Hutin

Lee

Glaunsinger

2013

J Virol

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Several viruses express factors to silence host gene expression via widespread mRNA degradation. This phenotype is the result of the coordinated activity of the viral endonuclease SOX and the cellular RNA degradation enzyme Xrn1 during lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection. While most cellular transcripts are highly downregulated, a subset of host mRNA escapes turnover via unknown mechanisms. One of the most prominent escapees is the interleukin 6 (IL-6) mRNA, which accumulates robustly during KSHV lytic infection and is not subjected to SOX-induced degradation. Here we reveal that the IL-6 mRNA contains a dominant, cis-acting ϳ100-nucleotide element within its 3= untranslated region (UTR) that renders it directly refractory to cleavage by SOX. This element specifically interacts with a cellular protein complex both in SOX-transfected cells and in KSHV-infected B cells. Using a directed RNA pulldown approach, we identified two components of this complex to be the AU-rich element (ARE) binding proteins AUF1 and HuR. Depletion of these proteins significantly reduced the protective capacity of the IL-6 RNA element in SOX-expressing cells. These findings suggest that SOX activity may be directly counteracted by select RNA regulatory complexes and reveal a novel mechanism contributing to the robust expression of IL-6 during KSHV replication.

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“…114 Finally, VEGF, in addition to its proangiogenic effects, impairs DC maturation and directly inhibits T-cell proliferation and cytotoxic activity. 115 Besides cytokines, chemokines primarily contribute to the recruitment of inhibitory immune cells. …”

Section: Tumor-associated Soluble Factorsmentioning

confidence: 99%

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies

Sun

Dotti

Savoldo

2016

Blood

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Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor–modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell–based therapies and the development of rational combination approaches.

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Suppression of dendritic cell differentiation through cytokines released by Primary Effusion Lymphoma cells

Cited by 41 publications

References 24 publications

Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells

Tyrosine kinase inhibitor tyrphostin AG490 triggers both apoptosis and autophagy by reducing HSF1 and Mcl-1 in PEL cells

An RNA Element in Human Interleukin 6 Confers Escape from Degradation by the Gammaherpesvirus SOX Protein

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies

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