Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein–Barr Virus and Kaposi’s Sarcoma-Associated Herpesvirus

Rivera-Soto, Ricardo; Damania, Blossom

doi:10.3389/fmicb.2019.01544

Cited by 16 publications

(16 citation statements)

References 340 publications

(343 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[16][17][18][19][20] Indeed, EBV orchestrates a variety of complex mechanism favouring the escape of lymphoma cells from anti-tumour immune responses while promoting the creation of niches in which tumour cells may find support for their growth and survival. [19][20][21][22] Computational methods such as GEP deconvolution allow high sensitivity discrimination of cell subsets within complex tissues, as tumours. 23 These approaches provide quantitative/ functional information also on rare tumour-infiltrating elements, offering the unprecedented opportunity of reanalysing available genomic data and identifying the immune signature.…”

Section: Introductionmentioning

confidence: 99%

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

Granai

Mundo

Akarca

et al. 2020

Preprint

View full text Add to dashboard Cite

BACKGROUND: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood.METHODS: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. RESULTS: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. CONCLUSION: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

Granai

Mundo

Akarca

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The constitutive association between EBV and BL, especially with endemic Burkitt lymphoma raises questions regarding the role of the virus in altering and actively shaping the tumour microenvironment [16][17][18][19][20]. Indeed, EBV orchestrates a variety of complex mechanism favouring the escape of lymphoma cells from antitumour immune responses while promoting the creation of niches in which tumour cells may find support for their growth and survival [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Granai

Mundo

Akarca

et al. 2020

Infect Agents Cancer

View full text Add to dashboard Cite

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. Results: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. Conclusion: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

show abstract

“…Viral IL-6-induced tubule formation is mediated through ITGB3. vIL-6 has been previously reported to aid in angiogenesis (26,27,39,40). Since KS is highly vascularized, we sought to determine if this was the case for vIL-6-expressing cells as well.…”

Section: Resultsmentioning

confidence: 99%

“…Through activation of transcription factor STAT3, vIL-6 induces cell proliferation (18,22,23) as well as migration (23)(24)(25). vIL-6 also induces angiogenesis and hematopoiesis, aiding in the growth of tumors (26,27).…”

mentioning

confidence: 99%

Kaposi’s Sarcoma-Associated Herpesvirus Viral Interleukin-6 Signaling Upregulates Integrin β3 Levels and Is Dependent on STAT3

Rivera-Soto

Dissinger

Damania

2020

J Virol

Self Cite

View full text Add to dashboard Cite

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of two B-cell lymphoproliferative diseases and Kaposi’s sarcoma, an endothelial-cell-driven cancer. KSHV viral interleukin-6 (vIL-6) is a viral homolog of human IL-6 (hIL-6) that is expressed in KSHV-associated malignancies. Previous studies have shown that the expression of the integrin β3 (ITGB3) subunit is induced upon KSHV infection. Here we report that KSHV vIL-6 is able to induce the expression of ITGB3 and increase surface expression of the αVβ3 integrin heterodimer. We demonstrated using small interfering RNA (siRNA) depletion and inhibitor studies that KSHV vIL-6 can increase ITGB3 by inducing STAT3 signaling. Furthermore, we found that secreted vIL-6 is capable of inducing ITGB3 in endothelial cells in a paracrine manner. Importantly, the ability to induce ITGB3 in endothelial cells seems to be specific to vIL-6, as overexpression of hIL-6 alone did not affect levels of this integrin. Our lab and others have previously shown that vIL-6 can induce angiogenesis, and we investigated whether ITGB3 was involved in this process. We found that siRNA depletion of ITGB3 in vIL-6-expressing endothelial cells resulted in a decrease in adhesion to extracellular matrix proteins. Moreover, depletion of ITGB3 hindered the ability of vIL-6 to promote angiogenesis. In conclusion, we found that vIL-6 can singularly induce ITGB3 and that this induction is dependent on vIL-6 activation of the STAT3 signaling pathway. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies: multicentric Castleman’s disease, primary effusion lymphoma, and Kaposi’s sarcoma. Kaposi’s sarcoma is a highly angiogenic tumor that arises from endothelial cells. It has been previously reported that KSHV infection of endothelial cells leads to an increase of integrin αVβ3, a molecule observed to be involved in the angiogenic process of several malignancies. Our data demonstrate that the KSHV protein viral interleukin-6 (vIL-6) can induce integrin β3 in an intracellular and paracrine manner. Furthermore, we showed that this induction is necessary for vIL-6-mediated cell adhesion and angiogenesis, suggesting a potential role of integrin β3 in KSHV pathogenesis and development of Kaposi’s sarcoma.

show abstract

Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein–Barr Virus and Kaposi’s Sarcoma-Associated Herpesvirus

Cited by 16 publications

References 340 publications

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Kaposi’s Sarcoma-Associated Herpesvirus Viral Interleukin-6 Signaling Upregulates Integrin β3 Levels and Is Dependent on STAT3

Contact Info

Product

Resources

About