Antigen Presentation by MHC-Dressed Cells

Nakayama, Masafumi

doi:10.3389/fimmu.2014.00672

Cited by 105 publications

(103 citation statements)

References 82 publications

(131 reference statements)

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“…Soluble tumor antigens from tumor cells are captured by antigen presenting cells (APCs), and then combined with major histocompatibility complex (MHC) class I molecules into complex which expressed on APCs. The T cell receptors (TCRs) recognize the complex and then promote the activation of CTLs which kill tumor cells by releasing perforin or promoting apoptosis [6, 43]. These previous studies were consistent with our results which showed that high level of CD8+ TILs correlated with better survival in EC in general.…”

Section: Discussionsupporting

confidence: 82%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8⁺ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3⁺ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57⁺ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3⁺, CD4⁺ and CD45RO⁺ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

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Section: Discussionsupporting

confidence: 82%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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“…Similar to the in vivo situation and consistent with a higher degree of LMP, IFNγ release by OT-I cells was greatly enhanced when Stat3 was absent from ovalbumin expressing tumor cells and markedly reduced upon treatment of OVA-CMT Stat3KD with the pan-cysteine protease inhibitor E64d (Figure 5E), further supporting the notion that LMP-dependent protease release may be involved in antigen processing in epithelial cells. Indeed, when H 2 O 2 challenged OVA-CMT Stat3KD or OVA-CMT scr cells were co-cultured with MACS-purified OT-I CD8 + T cells in the absence of CD11c + DCs, this was sufficient to elicit IFNγ secretion (Figure 5F), yet IFNγ production was greatly enhanced when increasing numbers of CD11c + DCs were added (Figure 5G) suggesting the transfer and presentation of MHC class I molecules via cross-dressing (Nakayama, 2015) rather than cross-presentation. To examine this possibility, we co-cultured ovalbumin-expressing CT26 colon tumor cells of BALB/c origin (OVA-CT26 Stat3KD and OVA-CT26 scr ) or haplo-identical OVA-CMT Stat3KD and OVA-CMT scr together with C57BL/6-derived DCs from WT or Tap1 -deficient mice along with OT-I CD8 T cells (Figure 5H).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, it was noted that, in addition to foreign protein, DCs can also take up complete antigen-MHC class I (and II) complexes and present them to T cells, a process termed “cross-dressing” (Nakayama, 2015). This process has been implicated in anti-tumor immunity as well as anti-viral host defense (Nakayama, 2015). …”

Section: Introductionmentioning

confidence: 99%

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis

Ziegler

Bollrath

Pallangyo

et al. 2018

Cell

100

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In colorectal cancer patients, a high density of cytotoxic CD8 T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8 T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8 T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer.

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“…Intercellular transfer of MHC is mediated by either cell contact-dependent trogocytosis or uptake of exosomes released by donor cells (20). To distinguish between these 2 mechanisms, BALB/c TEC labeled with CTxB and NOD thymic SIRPα + and CD8α + cDC were cultured using a transwell apparatus.…”

Section: Resultsmentioning

confidence: 99%

“…An additional and more direct process involves intercellular transfer of plasma membrane containing MHC-peptide complexes (pMHC) from live mTEC to DC (6, 10, 16, 18). This process has been referred to as “DC cross-dressing” and is mediated by at least 2 distinct mechanisms (reviewed in (19, 20)). The first, trogocytosis or “nibbling”, entails contact-dependent, intercellular transfer of pMHC embedded in plasma membrane, and occurs between lymphocytes and innate effectors in various contexts (21–23).…”

Section: Introductionmentioning

confidence: 99%

Thymic Dendritic Cell Subsets Display Distinct Efficiencies and Mechanisms of Intercellular MHC Transfer

Kroger

Spidale

Wang

et al. 2017

The Journal of Immunology

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Thymic dendritic cells (DC) delete self-Ag-specific thymocytes, and drive development of FoxP3-expressing immunoregulatory T cells. Unlike medullary thymic epithelial cells (mTEC), which express and present peripheral self-Ag, DC must acquire self-Ag to mediate thymic negative selection. One such mechanism entails the transfer of surface MHC-self peptide complexes from mTEC to thymic DC. Despite the importance of thymic DC “cross-dressing” in negative selection, the factors that regulate the process, and the capacity of different thymic DC subsets to acquire MHC and stimulate thymocytes are poorly understood. Here intercellular MHC transfer by thymic DC subsets was studied using a MHC-mismatch-based in vitro system. Thymic conventional DC (cDC) subsets SIRPα+ and CD8α+ readily acquired MHC class I and II from TEC but plasmacytoid DC (pDC) were less efficient. Intercellular MHC transfer was donor cell-specific; thymic DC readily acquired MHC from TEC plus thymic or splenic DC, whereas thymic or splenic B cells were poor donors. Furthermore DC origin influenced cross-dressing; thymic versus splenic DC exhibited an increased capacity to capture TEC-derived MHC, which correlated with direct expression of EpCAM by DC. Despite similar capacities to acquire MHC-peptide complexes, thymic CD8α+ cDC elicited increased T cell stimulation relative to SIRPα+ cDC. DC cross-dressing was cell-contact dependent and unaffected by lipid raft disruption of donor TEC. Furthermore, blocking PI3K signaling reduced MHC acquisition by thymic CD8α+ cDC and pDC but not SIRPα+ cDC. These findings demonstrate that multiple parameters influence the efficiency of and distinct mechanisms drive intercellular MHC transfer by thymic DC subsets.

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Antigen Presentation by MHC-Dressed Cells

Cited by 105 publications

References 82 publications

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis

Thymic Dendritic Cell Subsets Display Distinct Efficiencies and Mechanisms of Intercellular MHC Transfer

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