OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway

Jeannin, Pascale; Renno, Toufic; Goetsch, Liliane; Miconnet, Isabelle; Aubry, Jean‐Pierre; Delneste, Yves; Herbault, Nathalie; Baussant, Thierry; Magistrelli, Giovanni; Soulas, Caroline; Romero, Pedro; Cerottini, Jean‐Charles; Bonnefoy, Jean‐Yves

doi:10.1038/82751

Cited by 199 publications

(145 citation statements)

References 53 publications

(35 reference statements)

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“…These mechanisms may be employed to load exogenous antigen on MHC class I molecules in vitro and potentially also in vivo. Recently, Jeannin et al 117 showed that whole antigen coupled to a Klebsiella pneumoniae protein (kpOmpA ) specifically bound to a receptor on professional APCs and resulted in the delivery of antigen into the MHC class I presentation pathway. Simultaneous immunization with kpOmpA coupled to ovalbumin resulted in protection against a tumor challenge with ovalbumin -expressing tumor cells.…”

Section: Improving the Efficiency Of Cross -Primingmentioning

confidence: 99%

Principles of tumor immunosurveillance and implications for immunotherapy

Ochsenbein

2002

Cancer Gene Ther

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Although antigen loss variants, major histocompatibility ( MHC ) class I down -regulation, or the expression of inhibitory molecules may explain the failure of immunosurveillance against some tumors, this seems not to apply for many other solid peripheral or lymphohematopoietic tumors. Why then is immunosurveillance so ineffective and can it be improved? This review focuses on one important aspect of tumor immunity, namely the relevance of antigen dose and localization. Immune responses in vivo are induced in organized lymphoid tissues, i.e., in lymph nodes and spleen. The antigen dose that reaches secondary lymphoid organs over time is a crucial parameter that drives antiviral and antitumoral immune responses. Tumors use various strategies to prevent efficient presentation of their antigens in lymphoid organs. A major obstacle to the induction of an endogenous tumor -specific cytotoxic T lymphocyte ( CTL ) response is the inefficient presentation of tumor antigen on MHC class I molecules of professional antigenpresenting cells. Peripheral solid tumors that develop outside lymphoid organs are, therefore, often ignored by the immune system. In other situations, tumors -especially of lymphohematopoietic origin -may tolerize specific CTLs. Understanding tumor immunosurveillance is key to the design of efficient antitumor vaccines. Attempts to improve immunity to tumors include vaccination strategies to ( a ) provide the tumor antigen to secondary lymphoid organs using recombinant viruses or dendritic cells as carriers, ( b ) express costimulatory signals on tumor cells, or ( c ) improve the efficiency of cross -priming.

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Section: Improving the Efficiency Of Cross -Primingmentioning

confidence: 99%

Principles of tumor immunosurveillance and implications for immunotherapy

Ochsenbein

2002

Cancer Gene Ther

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“…Additionally, we set out to elucidate which mechanisms are responsible for these processes. To mimic a bacterial infection, DC were matured by a membrane fraction of K. pneumoniae (FMKp), which is a lysate of the outer membrane fraction of K. pneumoniae containing the DC-triggering agents LPS and outer membrane protein A (OmpA), which signal trough TLR4 and TLR2, respectively [20]. For its proven additional effect on upregulation of costimulatory molecules and modulation of cytokine secretion, IFN-g was added to the FMKp maturation cocktail [21].…”

Section: Introductionmentioning

confidence: 99%

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

et al. 2010

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Besides their role in destruction of altered self-cells, NK cells have been shown to potentiate T-cell responses by interacting with DC. To take advantage of NK-DC crosstalk in therapeutic DC-based vaccination for infectious diseases and cancer, it is essential to understand the biology of this crosstalk. We aimed to elucidate the in vitro mechanisms responsible for NK-cell recruitment and activation by DC during infection. To mimic bacterial infection, DC were exposed to a membrane fraction of Klebsiella pneumoniae, which triggers TLR2/4. DC matured with these bacterial fragments can actively recruit NK cells in a CCR5-dependent manner. An additional mechanism of DC-induced NK-cell recruitment is characterized by the induction of CCR7 expression on CD56 dim CD16 1 NK cells after physical contact with membrane fraction of K. pneumoniae-matured DC, resulting in an enhanced migratory responsiveness to the lymph node-associated chemokine CCL19. Bacterial fragment-matured DC do not only mediate NK-cell migration but also meet the prerequisites needed for augmentation of NK-cell cytotoxicity and IFN-c production, the latter of which contributes to Th1 polarization.Key words: CCR5 . CCR7 . NK-DC interaction . Th1 polarization Supporting Information available online Introduction NK cells are important effector cells in the innate immune response against virally infected or malignantly transformed cells and their cytotoxicity is regulated by a delicate balance of inhibitory and activating signals [1]. Recent studies suggest that the interplay between NK cells and DC, the specialized antigenpresenting cell of the innate immune system [2], is critical in shaping the adaptive immune response [3]. This concept originates from several lines of evidence including: the discovery of NK cells colocalizing with DC in the T-cell areas of lymph nodes [4,5], the coupling of NK-cell recruitment to lymph nodes Ã These authors contributed equally to this work. 3138with the induction of more potent Th1 skewing [3], and the identification of NK-cell subpopulations with helper properties [6]. Although the exact mechanisms of NK-DC interaction remain to be elucidated, increasing evidence supports the importance of bidirectional NK-DC crosstalk [7,8].On the one hand, NK-DC crosstalk is characterized by the capacity of activated NK cells to induce DC maturation with elevated IL-12p70 production and subsequently an increased capacity to induce Th1 and CTL responses [9]. This NK-induced DC maturation depends at least in part on soluble factors such as and as well as on engagement of the natural cytotoxicity triggering receptor 30 [12]. Moreover, NK cells control the quality of the adaptive immune response by natural cytotoxicity triggering receptor 30-mediated lysis of immature or inadequately matured DC [13], enabling only fully mature DC to migrate into lymph nodes and subsequently prime T cells. On the other hand, DC are able to induce NK-cell proliferation, augmentation of cytotoxicity and cytokine secretion [8]. The DC-induced modulati...

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“…The gene encoding the P40 from K. pneumoniae was provided by the Centre d'Immunologie Pierre Fabre (CIPF, Saint Julien en Genevois, France). [18][19][20][21] The human CD40L cDNA was purchased from InvivoGen (Cayla, Toulouse, France). The gene encoding the HN of the NDV was derived from plasmid p36/7-HN.…”

Section: Adenoviral Vectorsmentioning

confidence: 99%

“…18,19 P40 binds TLR2 on the surface of antigen-presenting cells (DCs and macrophages) and induces the phenotypic maturation of DCs, [18][19][20] secretion of interleukin (IL)-12 and the inflammatory cytokines IL-6, IL-8 and tumor necrosis factor (TNF)-a. P40 mixed with a tumor antigen peptide was shown to elicit tumor-specific CTL responses and to significantly delay the growth of B16F10 melanoma tumors implanted at the time of immunization. 21 Flagellin is the main component of the bacterial flagella and induces DC maturation and chemokine secretion by activating NF-kB through their interaction with TLR5.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated gene transfer of pathogen-associated molecular patterns for cancer immunotherapy

et al. 2008

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The delivery of stimulatory signals to dendritic cells (DCs) in the tumor microenvironment could be an effective means to break tumorinduced tolerance. The work presented here evaluates the immunostimulatory properties of pathogen-associated molecular patterns (PAMPs), microbial molecules which bind Toll-like receptors and deliver activating signals to immune cells, when expressed in tumor cells using adenoviral (Ad) vectors. In vitro, transduction of A549 tumor cells with Ad vectors expressing either flagellin from Listeria monocytogenes or P40 protein from Klebsiella pneumoniae induced the maturation of human monocyte-derived DCs in co-cultures. In mixed lymphocyte reactions (MLRs), Ad-flagellin and Ad-P40 transduction of tumor cells stimulated lymphocyte proliferation and the secretion of IFN-g. In vivo, these vectors were used either as stand-alone immunoadjuvants injected intratumorally or as vaccine adjuvants combined with a tumor antigen-expressing vector. When Ad-PAMPs were administered intratumorally to mice bearing subcutaneous syngeneic B16F0-CAR (cocksackie-adenovirus receptor) melanomas, tumor progression was transiently inhibited by Ad-P40. In a therapeutic vaccine setting, the combination of Ad-MUC1 and Ad-PAMP vectors injected subcutaneously delayed the growth of implanted RenCa-MUC1 tumors and improved tumor rejection when compared with vaccination with Ad-MUC1 alone. These results suggest that Ad-PAMPs could be effective immunoadjuvants for cancer immunotherapy.

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OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway

Cited by 199 publications

References 53 publications

Principles of tumor immunosurveillance and implications for immunotherapy

Principles of tumor immunosurveillance and implications for immunotherapy

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

Adenovirus-mediated gene transfer of pathogen-associated molecular patterns for cancer immunotherapy

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