scholarly journals Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Eiichi Hara ◽  
Yoshihisa Namiki ◽  
Toshifumi Ohkusa ◽  
...  

The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

2013 ◽  
Vol 210 (5) ◽  
pp. 1035-1047 ◽  
Author(s):  
Elodie Segura ◽  
Mélanie Durand ◽  
Sebastian Amigorena

Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ–resident CD8+ DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3+ DCs were recently shown to be the homologues of mouse CD8+ DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1+ DCs, BDCA3+ DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1+ and BDCA3+ DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ–resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
A. Jiménez-Periáñez ◽  
B. Abos Gracia ◽  
J. López Relaño ◽  
C. M. Diez-Rivero ◽  
P. A. Reche ◽  
...  

The mesoporous silicon microparticles (MSMPs) are excellent vehicles for releasing molecules inside the cell. The aim of this work was to use MSMPs to deliver viral specific MHC class I restricted epitopes into human antigen presenting cells (monocyte derived dendritic cells, MDDCs) to facilitate their capture, processing, and presentation to CD8+ (cytotoxic) T lymphocytes. We show for the first time that MSMPs vehiculation of antigenic peptides enhances their MHC class I presentation by human MDDCs to CD8 T lymphocytes.


2013 ◽  
Vol 144 (5) ◽  
pp. S-873
Author(s):  
Kazuki Takakura ◽  
Shigeo Koido ◽  
Sadamu Homma ◽  
Akitaka Takahara ◽  
Shunichi Odahara ◽  
...  

2006 ◽  
Vol 177 (4) ◽  
pp. 2131-2137 ◽  
Author(s):  
Giandomenica Iezzi ◽  
Andrea Boni ◽  
Elena Degl’Innocenti ◽  
Matteo Grioni ◽  
Maria T. S. Bertilaccio ◽  
...  

2019 ◽  
Vol 68 (10) ◽  
pp. 1605-1619 ◽  
Author(s):  
Yuji Tomita ◽  
Eri Watanabe ◽  
Masumi Shimizu ◽  
Yasuyuki Negishi ◽  
Yukihiro Kondo ◽  
...  

Abstract The main effectors in tumor control are the class I MHC molecule-restricted CD8+ cytotoxic T lymphocytes (CTLs). Tumor-specific CTL induction can be regulated by dendritic cells (DCs) expressing both tumor-derived epitopes and co-stimulatory molecules. Immunosuppressive tolerogenic DCs, having down-regulated co-stimulatory molecules, are seen within the tumor mass and can suppress tumor-specific CTL induction. The tolerogenic DCs expressing down-regulated XCR1+CD141+ appear to be induced by tumor-derived soluble factors or dexamethasone, while the immunogenic DCs usually express XCR1+CD141+ molecules with a cross-presentation function in humans. Thus, if tolerogenic DCs can be reactivated into immunogenic DCs with sufficient co-stimulatory molecules, tumor-specific CD8+ CTLs can be primed and activated in vivo. In the present study, we converted human tolerogenic CD141+ DCs with enhanced co-stimulatory molecule expression of CD40, CD80, and CD86 through stimulation with non-toxic mycobacterial lipids such as mycolic acid (MA) and lipoarabinomannan (LAM), which synergistically enhanced both co-stimulatory molecule expression and interleukin (IL)-12 secretion by XCR1+CD141+ DCs. Moreover, MA and LAM-stimulated DCs captured tumor antigens and presented tumor epitope(s) in association with class I MHCs and sufficient upregulated co-stimulatory molecules to prime naïve CD3+ T cells to become CD8+ tumor-specific CTLs. Repeat CD141+ DC stimulation with MA and LAM augmented the secretion of IL-12. These findings provide us a new method for altering the tumor environment by converting tolerogenic DCs to immunogenic DCs with MA and LAM from Mycobacterium tuberculosis.


2006 ◽  
Vol 95 (01) ◽  
pp. 22-28 ◽  
Author(s):  
Annalisa Del Prete ◽  
Massimo Locati ◽  
Karel Otero ◽  
Elena Riboldi ◽  
Alberto Mantovani ◽  
...  

SummaryDendritic cells (DC) are professional antigen presenting cells which playa pivotal role in the activation of adaptive immunity. Tissue invasion by pathogens induces the recruitment of blood DC to the site of infection and contributes to their subsequent migration to secondary lymphoid organs. This complex process relies on the expression and regulation of receptors for chemotactic factors on the surface of migrating DC and on the activation of adhesion molecules which allow DC to properly interact with both blood and lymphatic vessels. In the absence of correct tissue localization, DC fail to promote proper immune responses. Therefore, the interaction of DC with endothelial cells represents a fundamental step for DC biology.


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