Serine Protease Inhibitor 6 Is Required To Protect Dendritic Cells from the Kiss of Death

Lovo, Elena; Zhang, Manling; Wang, Lihui; Ashton‐Rickardt, Philip G.

doi:10.4049/jimmunol.1102667

Cited by 27 publications

(29 citation statements)

References 34 publications

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“…[39][40][41] We and others have shown that only a small fraction (,1%) of locally inoculated DCs can migrate to the draining lymph nodes, whereas most remain at the site of immunization. 13,42,43 IV-delivered DCs are also insufficient to traffic to the spleen and lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

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Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Zhang

Bridle

Chen

et al. 2013

Blood

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Section: Discussionmentioning

confidence: 99%

“…The H-2D b -restricted peptide of LCMV-GP (GP [33][34][35][36][37][38][39][40][41] ; KAVYNFATM) was purchased from the Dalton Chemical Laboratory (Toronto, Canada). Peptides were dissolved in distilled water and stored at 220°C.…”

Section: Peptidesmentioning

confidence: 99%

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Zhang

Bridle

Chen

et al. 2013

Blood

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“…*p , 0.05, **p , 0.01, ***p . 0.001. or that these cells may have received survival signals through interactions with Ag-specific T cells (45,46). Regardless, the crucial role of langerin + CD8a + DCs in cross-priming is not simply because they are the only cells capable of cross-presentation, because Ag was effectively processed and presented in their absence (Fig.…”

Section: Cd8amentioning

confidence: 99%

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Osmond

Farrand

Painter

et al. 2015

The Journal of Immunology

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The function of dendritic cells (DCs) can be modulated through multiple signals, including recognition of pathogen-associated molecular patterns, as well as signals provided by rapidly activated leukocytes in the local environment, such as innate-like T cells. In this article, we addressed the possibility that the roles of different murine DC subsets in cross-priming CD8+ T cells can change with the nature and timing of activatory stimuli. We show that CD8α+ DCs play a critical role in cross-priming CD8+ T cell responses to circulating proteins that enter the spleen in close temporal association with ligands for TLRs and/or compounds that activate NKT cells. However, if NKT cells are activated first, then CD8α− DCs become conditioned to respond more vigorously to TLR ligation, and if triggered directly, these cells can also contribute to priming of CD8+ T cell responses. In fact, the initial activation of NKT cells can condition multiple DC subsets to respond more effectively to TLR ligation, with plasmacytoid DCs making more IFN-α and both CD8α+ and CD8α− DCs manufacturing more IL-12. These results suggest that different DC subsets can contribute to T cell priming if provided appropriately phased activatory stimuli, an observation that could be factored into the design of more effective vaccines.

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“…1: premetastatic Results from one experiment in the study appears to be in favor of the idea that myeloid cells presenting activated STAT3 have some level of intrinsic resistance to CTL killing, as BM-derived macrophages stimulated by TCM and pulsed with the OVA peptide in vitro were less efficiently killed when they were STAT3-positive rather than when STAT3-deficient [15]. Interestingly, BMderived DCs have been previously reported to acquire resistance to granzyme B-dependent killing by CD8 + T cells, through the induction of the serpin serine protease inhibitor 6 (SPI-6) [18,19]. In that case, the acquired resistance of DC is thought to favor a sustained activation and expansion of immune effector cells.…”

mentioning

confidence: 99%

“…Interestingly, BMderived DCs have been previously reported to acquire resistance to granzyme B-dependent killing by CD8 + T cells, through the induction of the serpin serine protease inhibitor 6 (SPI-6) [18,19]. In that case, the acquired resistance of DC is thought to favor a sustained activation and expansion of immune effector cells.…”

mentioning

confidence: 99%

Silence STAT3 in the procancer niche…and activate CD8⁺ T cells to kill premetastatic myeloid intruders

Auphan-Anezin

Schmitt-Verhulst

2015

Eur J Immunol

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To efficiently counter tumor development, CD8 + T cells need to be activated in the tumor draining lymph node (TDLN) by DCs presenting tumor antigen (TA), a process that requires the capacity of DCs to "cross-present" the TA. In addition, the DCs need to be induced to differentiate into the appropriate stimulatory mode, with high expression of costimulatory molecules and MHC molecules (reviewed in [1]). If this initial interaction between the DC and the CD8 + T cell is successful, the CD8 + T cells to which the TA is presented subsequently differentiate into CTLs and acquire expression of effector molecules such as granzyme B and perforin, Correspondence: Dr. Anne-Marie Schmitt-Verhulst e-mail: verhulst@ciml.univ-mrs.fr the capacity to produce IFN-γ and also express surface molecules that permit their migration toward the tumor site. Although evidence for the successful elimination of primary tumors by CD8 + T cells exists in some experimental settings, as exemplified by the immunoediting occurring in chemically induced carcinomas in mice [2], in most cases T cells are ineffective at clearing tumors, notably as a result of the multiple immunosuppressive pathways present in the tumor environment [3,4].Recent evidence suggests a major role for the activation of the "transcription factor signal transducer and activator of transcription 3" (STAT3) in the induction and maintenance of a procarcinogenic, immunosuppressive tumor microenvironment (reviewed in [5]). In particular, oncogene-induced production of inflammatory mediators (such as IL-6, IL-10, and VEGF) by the tumor itself promotes STAT3 activation, causing an increase in both tumor proliferation and survival, and tumor-derived inflammatory cytokines (such as IL-6, -10, -11, -17, -21, -23; VEGF) that constitute STAT3 amplifying loops that further shape the tumor microenvironment [5,6]. One such amplifying loop comprises the recruitment and expansion of myeloid-derived cells with immune-suppressive activity to the microenvironment, which has been shown to be critical for disease progression and resistance to therapy [7,8]. These immune-suppressive, myeloid-derived cells are an heterogeneous population of immature myeloid cells that normally develop as intermediates during myelopoiesis in the bone marrow, but which were found to accumulate in certain pathological situations including cancer in both humans and mice [9,10]. Inhibition of T-cell function by immune-suppressive, myeloid-derived cells has been shown to be mediated by several mechanisms, including expression of enzymes affecting amino acid metabolism, such as the expression of arginase I by blood-derived myeloid cells in breast cancer patients [9,10]. Additionally, several studies have implicated soluble factors (VEGF, TGF-β, S100 inflammatory chemokines) secreted by the primary tumor in the recruitment of VEGFR1 + bone marrowderived hematopoietic progenitor cells [11] and Mac1 + myeloid cells [12] thereby providing an optimal "soil" for tumor cells to survive and to colonize secondary sites for metast...

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Serine Protease Inhibitor 6 Is Required To Protect Dendritic Cells from the Kiss of Death

Cited by 27 publications

References 34 publications

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Silence STAT3 in the procancer niche…and activate CD8⁺ T cells to kill premetastatic myeloid intruders

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Serine Protease Inhibitor 6 Is Required To Protect Dendritic Cells from the Kiss of Death

Cited by 27 publications

References 34 publications

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Silence STAT3 in the procancer niche…and activate CD8+ T cells to kill premetastatic myeloid intruders

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Product

Resources

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Silence STAT3 in the procancer niche…and activate CD8⁺ T cells to kill premetastatic myeloid intruders