scholarly journals Vesicular Stomatitis Virus-induced Immune Suppressor Cells Generate Antagonism Between Intratumoral Oncolytic Virus and Cyclophosphamide

2011 ◽  
Vol 19 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Candice Willmon ◽  
Rosa M Diaz ◽  
Phonphimon Wongthida ◽  
Feorillo Galivo ◽  
Timothy Kottke ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Oncolytic Virus ◽  
Suppressor Cells ◽  
Immune Suppressor Cells ◽  
Vesicular Stomatitis ◽  
Immune Suppressor

scholarly journals Myeloid-derived suppressor cells and the pathogenesis of human immunodeficiency virus infection

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Mahmoud Mohammad Yaseen ◽  
Nizar Mohammad Abuharfeil ◽  
Homa Darmani
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Hiv Infection ◽  
Immune Activation ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Chronic Immune Activation ◽  
Immune Suppressor Cells ◽  
Immunodeficiency Virus ◽  
Immune Suppressor

There are several mechanisms by which human immunodeficiency virus (HIV) can mediate immune dysfunction and exhaustion during the course of infection. Chronic immune activation, after HIV infection, seems to be a key driving force of such unwanted consequences, which in turn worsens the pathological status. In such cases, the immune system is programmed to initiate responses that counteract unwanted immune activation, for example through the expansion of myeloid-derived suppressor cells (MDSCs). Although the expansion of immune suppressor cells in the setting of systemic chronic immune activation, in theory, is expected to contain immune activation, HIV infection is still associated with a remarkably high level of biomarkers of immune activation. Paradoxically, the expansion of immune suppressor cells during HIV infection can suppress potent anti-viral immune responses, which in turn contribute to viral persistence and disease progression. This indicates that HIV hijacks not only immune activation but also the immune regulatory responses to its advantage. In this work, we aim to pave the way to comprehend how such unwanted expansion of MDSCs could participate in the pathology of acute/primary and chronic HIV infection in humans, as well as simian immunodeficiency virus infection in rhesus macaques, according to the available literature.

scholarly journals Vesicular Stomatitis Virus Oncolysis of T Lymphocytes Requires Cell Cycle Entry and Translation Initiation

2008 ◽  
Vol 82 (12) ◽  
pp. 5735-5749 ◽  
Author(s):  
Stephanie Oliere ◽  
Meztli Arguello ◽  
Thibault Mesplede ◽  
Vanessa Tumilasci ◽  
Peyman Nakhaei ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
T Lymphocytes ◽  
Vesicular Stomatitis Virus ◽  
Oncolytic Virus ◽  
Protein Translation ◽  
Lymphocytic Leukemia ◽  
Activated T Cells ◽  
Cell Cycle Entry ◽  
Vesicular Stomatitis

ABSTRACT Vesicular stomatitis virus (VSV) is a candidate oncolytic virus that replicates and induces cell death in cancer cells while sparing normal cells. Although defects in the interferon antiviral response facilitate VSV oncolysis, other host factors, including translational and growth regulatory mechanisms, also appear to influence oncolytic virus activity. We previously demonstrated that VSV infection induces apoptosis in proliferating CD4+ T lymphocytes from adult T-cell leukemia samples but not in resting T lymphocytes or primary chronic lymphocytic leukemia cells that remain arrested in G0. Activation of primary CD4+ T lymphocytes with anti-CD3/CD28 is sufficient to induce VSV replication and cell death in a manner dependent on activation of the MEK1/2, c-Jun NH2-terminal kinase, or phosphatidylinositol 3-kinase pathway but not p38. VSV replication is specifically impaired by the cell cycle inhibitor olomoucine or rapamycin, which induces early G1 arrest, but not by aphidicolin or Taxol, which blocks at the G11S or G21M phase, respectively; this result suggests a requirement for cell cycle entry for efficient VSV replication. The relationship between increased protein translation following G0/G1 transition and VSV permissiveness is highlighted by the absence of mTOR and/or eIF4E phosphorylation whenever VSV replication is impaired. Furthermore, VSV protein production in activated T cells is diminished by small interfering RNA-mediated eIF4E knockdown. These results demonstrate that VSV replication in primary T lymphocytes relies on cell cycle transition from the G0 phase to the G1 phase, which is characterized by a sharp increase in ribogenesis and protein synthesis.

scholarly journals Ruxolitinib and Polycation Combination Treatment Overcomes Multiple Mechanisms of Resistance of Pancreatic Cancer Cells to Oncolytic Vesicular Stomatitis Virus

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Sébastien A. Felt ◽  
Gaith N. Droby ◽  
Valery Z. Grdzelishvili
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Vesicular Stomatitis Virus ◽  
Oncolytic Virus ◽  
Ductal Adenocarcinoma ◽  
Mechanisms Of Resistance ◽  
Pdac Cell ◽  
Ldl Uptake ◽  
Vesicular Stomatitis ◽  
Pdac Cell Line

ABSTRACT Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV). Although VSV is effective against a majority of pancreatic ductal adenocarcinoma cell (PDAC) cell lines, some PDAC cell lines are highly resistant to VSV, and the mechanisms of resistance are still unclear. JAK1/2 inhibitors (such as ruxolitinib and JAK inhibitor I) strongly stimulate VSV replication and oncolysis in all resistant cell lines but only partially improve the susceptibility of resistant PDACs to VSV. VSV tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication rather than on receptor specificity, with several ubiquitously expressed cell surface molecules playing a role in VSV attachment to host cells. However, as VSV attachment to PDAC cells has never been tested before, here we examined if it was possibly inhibited in resistant PDAC cells. Our data show a dramatically weaker attachment of VSV to HPAF-II cells, the most resistant human PDAC cell line. Although sequence analysis of low-density lipoprotein (LDL) receptor (LDLR) mRNA did not reveal any amino acid substitutions in this cell line, HPAF-II cells displayed the lowest level of LDLR expression and dramatically lower LDL uptake. Treatment of cells with various statins strongly increased LDLR expression levels but did not improve VSV attachment or LDL uptake in HPAF-II cells. However, LDLR-independent attachment of VSV to HPAF-II cells was dramatically improved by treating cells with Polybrene or DEAE-dextran. Moreover, combining VSV with ruxolitinib and Polybrene or DEAE-dextran successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. IMPORTANCE Oncolytic virus (OV) therapy is an anticancer approach that uses viruses that selectively infect and kill cancer cells. This study focuses on oncolytic vesicular stomatitis virus (VSV) against pancreatic ductal adenocarcinoma (PDAC) cells. Although VSV is effective against most PDAC cells, some are highly resistant to VSV, and the mechanisms are still unclear. Here we examined if VSV attachment to cells was inhibited in resistant PDAC cells. Our data show very inefficient attachment of VSV to the most resistant human PDAC cell line, HPAF-II. However, VSV attachment to HPAF-II cells was dramatically improved by treating cells with polycations. Moreover, combining VSV with polycations and ruxolitinib (which inhibits antiviral signaling) successfully broke the resistance of HPAF-II cells to VSV by simultaneously improving VSV attachment and replication. We envision that this novel triple-combination approach could be used in the future to treat PDAC tumors that are highly resistant to OV therapy.

scholarly journals Oncolytic Virus with Attributes of Vesicular Stomatitis Virus and Measles Virus in Hepatobiliary and Pancreatic Cancers

2020 ◽  
Vol 18 ◽  
pp. 546-555
Author(s):  
Bolni Marius Nagalo ◽  
Camilo Ayala Breton ◽  
Yumei Zhou ◽  
Mansi Arora ◽  
James M. Bogenberger ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Measles Virus ◽  
Oncolytic Virus ◽  
Pancreatic Cancers ◽  
Vesicular Stomatitis

scholarly journals Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells

2017 ◽  
Vol 67 (3) ◽  
pp. 483-494 ◽  
Author(s):  
Veronika Bachanova ◽  
Dhifaf Sarhan ◽  
Todd E. DeFor ◽  
Sarah Cooley ◽  
Angela Panoskaltsis-Mortari ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Hodgkin Lymphoma ◽  
Suppressor Cells ◽  
Killer Cells ◽  
Non Hodgkin Lymphoma ◽  
Immune Suppressor Cells ◽  
Low Levels ◽  
Immune Suppressor

scholarly journals Lower Survival and Increased Circulating Suppressor Cells in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma with Deficit of Vitamin D Levels Using R-GDP Plus Lenalidomide (R2-GDP): Results from the R2-GDP-GOTEL Trial

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4622
Author(s):  
Carlos Jiménez-Cortegana ◽  
Pilar M. Sánchez-Martínez ◽  
Natalia Palazón-Carrión ◽  
Esteban Nogales-Fernández ◽  
Fernando Henao-Carrasco ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Cell Populations ◽  
Large B Cell Lymphoma ◽  
Immune Suppressor Cells ◽  
Vitamin D Levels ◽  
Immune Suppressor ◽  
Large B Cell

The search of prognostic factors is a priority in diffuse large B-cell lymphoma (DLBCL) due to its aggressiveness. We have recently found that the level of circulating MDSCs is a good marker of survival in a translational study based on a trial (EudraCT Number: 2014-001620-29), using lenalidomide combined with R-GDP (rituximab plus gemcitabine, cisplatin, and dexamethasone). Since Vitamin D is a known immunomodulator, we have studied blood levels of these cell populations comparing patients with deficit of vitamin D levels (<15 ng/mL with those with normal levels >15 ng/mL. Mann–Whitney U test was used to compare cells distributions between groups, Wilcoxon test to compare cells distribution at different times and Spearman test to measure the association between cell populations. Patients with vitamin D deficit maintained the increased level of immune suppressor cells, whereas we observed a depletion of all immune suppressor cells in patients with normal vitamin D levels. In conclusion, we have confirmed the importance of vitamin D in the response to treatment in R/R DLBCL, suggesting that vitamin D deficit may be involved in the immune deficit of these patients, and thus, vitamin D supplementation in these patients may help to obtain a better response, warranting further investigation.

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