Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

2014 ◽  
Author(s):  
David J. Chung
2020 ◽  
Author(s):  
Marco Jost ◽  
Amy N. Jacobson ◽  
Jeffrey A. Hussmann ◽  
Giana Cirolia ◽  
Michael A. Fischbach ◽  
...  

AbstractDendritic cells (DCs) regulate processes ranging from antitumor and antiviral immunity to host-microbe communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses. Here, we develop a CRISPR/Cas9 genome editing method for human monocyte-derived DCs (moDCs) that mediates knockouts with a median efficiency of >93% across >300 genes. Using this method, we perform genetic screens in moDCs, identifying mechanisms by which DCs tune responses to lipopolysaccharides from the human microbiome. In addition, we reveal donor-specific responses to lipopolysaccharides, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify genes that control this specificity, highlighting the potential of our method to pinpoint determinants of inter-individual variation in immune responses. Our work sets the stage for a systematic dissection of the immune signaling at the host-microbiome interface and for targeted engineering of DCs for neoantigen vaccination.


2018 ◽  
Vol 6 (4) ◽  
pp. 88 ◽  
Author(s):  
Sandra Solano-Gálvez ◽  
Sonia Tovar-Torres ◽  
María Tron-Gómez ◽  
Ariane Weiser-Smeke ◽  
Diego Álvarez-Hernández ◽  
...  

Dendritic cells (DCs) are a type of cells derived from bone marrow that represent 1% or less of the total hematopoietic cells of any lymphoid organ or of the total cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous population of cells localized in different tissues where they act as sentinels continuously capturing antigens to present them to T cells. Dendritic cells are uniquely capable of attracting and activating naïve CD4+ and CD8+ T cells to initiate and modulate primary immune responses. They have the ability to coordinate tolerance or immunity depending on their activation status, which is why they are also considered as the orchestrating cells of the immune response. The purpose of this review is to provide a general overview of the current knowledge on ontogeny and subsets of human dendritic cells as well as their function and different biological roles.


2003 ◽  
Vol 21 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Mathew H. Chung ◽  
Rishab K. Gupta ◽  
Eddy Hsueh ◽  
Richard Essner ◽  
Wei Ye ◽  
...  

Purpose: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (≥ 4 mm) primary cutaneous melanoma. Patients and Methods: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course. Results: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P = .184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P = .0006 and .006, respectively) but not with maximal IgG response (P = .73 and .95, respectively). Neither response predicted survival in the observation group. Conclusion: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.


2015 ◽  
Vol 45 (3) ◽  
pp. 162-166 ◽  
Author(s):  
Yo Seph Park ◽  
Jeong-Hwan Lee ◽  
Jin-Yeon Park ◽  
Han Sung Hwang ◽  
Martin Zenke ◽  
...  

Diabetes ◽  
2010 ◽  
Vol 59 (5) ◽  
pp. 1182-1191 ◽  
Author(s):  
B. M. Schulte ◽  
M. Kramer ◽  
M. Ansems ◽  
K. H. W. Lanke ◽  
N. van Doremalen ◽  
...  

2008 ◽  
Vol 21 (4) ◽  
pp. 929-939 ◽  
Author(s):  
B. Buttari ◽  
E. Profumo ◽  
R. Mancinelli ◽  
U. Cesta Incani ◽  
M.E. Tosti ◽  
...  

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-α and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.


2009 ◽  
Vol 136 (5) ◽  
pp. A-313
Author(s):  
Shigeo Koido ◽  
Eiichi Hara ◽  
Sadamu Homma ◽  
Hideo Komita ◽  
Akitaka Takahara ◽  
...  

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