Kataloganreicherung auf Exemplarebene oder Exemplaranreicherung auf Katalogebene? Mit der Bibliothek Wendelin Schmidt-Dengler auf dem Weg zum Katalog 2.0

Catalogue enrichment by a devious route (translation of the title). This article describes the challenges while searching for ways to incorporate information that is specific to certain copies into bibliographic records. Based on the handling of autographs and enclosures of the bequest library of professor for German philology Wendelin Schmidt-Dengler in the online catalogue of the Vienna University Library we suggest a possible solution

Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions

The tumor microenvironment (TME) is a critical regulator of tumor growth, progression, and metastasis. Since immune cells represent a large fraction of the TME, they play a key role in mediating pro- and anti-tumor immune responses. Immune escape, which suppresses anti-tumor immunity, enables tumor cells to maintain their proliferation and growth. Numerous mechanisms, which have been intensively studied in recent years, are involved in this process and based on these findings, novel immunotherapies have been successfully developed. Here, we review the composition of the TME and the mechanisms by which immune evasive processes are regulated. In detail, we describe membrane-bound and soluble factors, their regulation, and their impact on immune cell activation in the TME. Furthermore, we give an overview of the tumor/antigen presentation and how it is influenced under malignant conditions. Finally, we summarize novel TME-targeting agents, which are already in clinical trials for different tumor entities

IFNγ-induced expression of IDO by MSCs is necessary to inhibit Vδ2+ cell proliferation.

<p>(A) Lentiviral-mediated shRNA transduction of MSCs was used to knock down IDO (MSC-IDOi). Quantification of IDO mRNA by Real-Time qPCR was done in MSC-pLV, MSC-IFNγRi and MSC-IDOi. Relative expression was normalized to MSC-transduced with the empty vector (B) Representative flow cytometric analysis of activated Vδ2+ cells after five days of co-culture with transduced MSCs. Vδ2+ cells expand more in the presence of MSC-IDOi compared to MSC-pLV. (C) Specific silencing of IDO augments the number of Vδ2+ cells after five days of co-culture. Results show the means ± S.D. of triplicate samples. **P ≤ 0.01. (D) Representative proliferation analysis of CFSE-labeled Vδ2+ cells performed at day five of co-culture with either MSC-IDOi (white) or empty vector (grey). Proliferation index of Vδ2+ cells in co-culture with MSCs silenced with shRNA for IDO is higher compared to MSC transduced with the empty vector (right panel), similar to the results obtained with MSC-IFNγRi. Results show the means ± S.D. of triplicate samples. *P ≤ 0.05. (E) Co-culture of Vδ2+ cells and MSC-IDOi gives rise to more intracellular IFNγ production of Vδ2+ cells compared to a co-culture with MSC-pLV after 12h. Results show the means ± S.D. of triplicate samples. **P ≤ 0.01. Representative flow cytometric analysis of IFNγ production in Vδ2+ cells co-cultured with MSC-IDOi after 12h of activation (right panel).</p

Interfering with the IFNγ pathway in MSCs by specific silencing of the IFNγR and analysis of apoptosis in MSCs.

<p>(A) Lentiviral-mediated shRNA transduction of MSCs was used to knock down the IFNγR. MSCs were transduced either with the empty vector (MSC-pLV) (upper panel) as control or with an IFNγR specific shRNA (MSC-IFNγRi) (lower panel). GFP expression in transduced cells was analysed four days after transduction by Flow Cytometry. (B) The efficiency of gene silencing was quantified by Real-Time qPCR in MSCs transduced either with the empty vector or with the one specific for IFNγRi. mRNA expression for IFNγR was significantly reduced in MSC-IFNγRi compared to MSC-pLV. Relative expression was normalized to the empty vector (MSC-pLV). (C) Transduction of MSCs does not lead to apoptotic cell death. Flow cytometric analysis of apoptotic cells (APC positive cells) in MSC-pLV (left) and MSC-IFNγRi (right) by AnnexinV staining 6 days after transduction.</p

MSCs inhibit the expansion of Vδ2+ cells by soluble mediators.

<p>(A) The presence of MSCs reduces the expansion of Vδ2+ cells. Representative flow cytometric analysis of Vδ2+ cells activated from whole PBMC by HDMAPP and rh-IL2 for seven days in the absence (left panel) or presence (right panel) of MSCs. (B) Increasing ratios of MSC:MNC diminish the inhibitory effects of MSCs on Vδ2+ cell proliferation. Results show the means ± S.D. of triplicate samples. (C) Total PBMCs were labeled with CFSE and activated by HDMAPP and rh-IL2. Analysis of Vδ2+ cell proliferation in the presence (white) or absence (grey) of MSCs was performed after five days by Flow Cytometry. The presence of MSCs lowers the proliferation index of Vδ2+ cells (right panel). Results show the means ± S.D. of triplicate samples. ***P ≤ 0.001. (D) Analysis of the percentage of Vδ2+ cells cultured in cell-to-cell contact or in a transwell system in the presence/absence of MSCs. Vδ2+ cell expansion is inhibited in the same way in both systems indicating that soluble factors are responsible for immunoregulation. Results show the means ± S.D. of triplicate samples.</p

IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells - Fig 4

<p>Interfering with the IFNγ pathway in MSCs can partially restore Vδ2+ cell proliferation (A) Comparison of Vδ2+ cell expansion in co-culture with either MSC-pLV (left panel) or MSC-IFNγRi (right panel). Representative Flow cytometric analysis of Vδ2+ cells at day five. (B) Specific silencing of the IFNγR augments the number of Vδ2+ cells after five days of co-culture. Results show the means ± S.D. of triplicate samples. ***P ≤ 0.001. (C) Total PBMCs were labeled with CFSE and flow cytometric analysis of Vδ2+ cell proliferation was performed five days after co-culture with either MSC-IFNγRi (white) or MSC-pLV (grey). Proliferation index of Vδ2+ cells in co-culture with MSC silenced with shRNA for IFNγR is higher compared to MSC transduced with the empty vector (right panel). Results show the means ± S.D. of triplicate samples. *P ≤ 0.05. (D) Co-culture of Vδ2+ cells and MSC-IFNγRi gives rise to more intracellular IFNγ production by Vδ2+ cells compared to a co-culture with MSC-pLV, especially after 12h. Results show the means ± S.D. of triplicate samples. *P ≤ 0.05. Representative flow cytometric analysis of IFNγ production in Vδ2+ cells after 12h of activation (right panel).</p

Immunoregulation is subject to a critical time window and IFNγ signalling in MSC is required for the inhibition of Vδ2+ proliferation.

<p>(A) Analysis of intracellular IFNγ production in activated Vδ2+ cells at early time points. Results show the means ± S.D. of triplicate samples. *P ≤ 0.05. (B) Representative analysis of intracellular IFNγ production by Vδ2+ cells in the absence (upper panel) or presence (lower panel) of MSCs after 12h of co-culture. (C) Inhibition of proliferation of Vδ2+ cells by MSCs in a critical time window. Whole PBMCs were pre-activated for the indicated times and subsequently co-cultured with MSCs. Percentage of Vδ2+ cells were determined by Flow Cytometry five days after plating. Results show the means ± S.D. of triplicate samples.</p