Evidence map›Paper›PMID 34189679›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2021

Cystatin F acts as a mediator of immune suppression in glioblastoma.

Emanuela Senjor, Milica Perišić Nanut, Barbara Breznik, Ana Mitrović, Jernej Mlakar, Ana Rotter, Andrej Porčnik, Tamara Lah Turnšek, Janko Kos

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Emanuela SenjorDepartment of Biotechnology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia.
Milica Perišić NanutDepartment of Biotechnology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia.
Barbara BreznikDepartment of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, SI-1000, Ljubljana, Slovenia.
Ana MitrovićDepartment of Biotechnology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia.
Jernej MlakarInstitute of Pathology, Medical Faculty, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia.
Ana RotterDepartment of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, SI-1000, Ljubljana, Slovenia.
Andrej PorčnikDepartment of Neurosurgery, University Clinical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Tamara Lah TurnšekDepartment of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, SI-1000, Ljubljana, Slovenia.
Janko KosDepartment of Biotechnology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia. janko.kos@ffa.uni-lj.si.ORCID http://orcid.org/0000-0002-4228-3518
National Institute of Biology · SIUniversity of Ljubljana · SIJožef Stefan Institute · SILjubljana University Medical Centre · SI

Funding

European Program of Cross-Boarder Cooperation for Slovenia-Italy Interreg TRANS-GLIOMASlovenian Research Agency J3-2516Slovenian Research Agency P1-0245Slovenian Research Agency P4-0127, J4-1776Slovenian Research Agency Z3-1870
6 · The paper itself

Abstract

purposeGlioblastoma, the most aggressive type of brain cancer, is composed of heterogeneous populations of differentiated cells, cancer stem cells and immune cells. Cystatin F, an endogenous inhibitor of lysosomal cysteine peptidases, regulates the function of cytotoxic immune cells. The aim of this study was to determine which type of cells expresses cystatin F in glioblastoma and to determine the role of cystatin F during disease progression.

methodsRT-qPCR and immunohistochemistry were used to determine cystatin F mRNA and protein levels in glioblastoma tissue samples. The internalization of cystatin F was analyzed by Western blotting. Enzyme kinetics, real time invasion and calcein release cytotoxicity assays were used to assess the role of internalized cystatin F.

resultsWe found that cystatin F was not expressed in non-cancer brain tissues, but that its expression increased with glioma progression. In tumor tissues, extensive staining was observed in cancer stem-like cells and microglia/monocytes, which secrete cystatin F into their microenvironment. In trans activity of cystatin F was confirmed using an in vitro glioblastoma cell model. Internalized cystatin F affected cathepsin L activity in glioblastoma cells and decreased their invasiveness. In addition, we found that cystatin F decreased the susceptibility of glioblastoma cells to the cytotoxic activity of natural killer (NK) cells.

conclusionsOur data implicate cystatin F as a mediator of immune suppression in glioblastoma. Increased cystatin F mRNA and protein levels in immune, glioblastoma and glioblastoma stem-like cells or trans internalized cystatin F may have an impact on decreased susceptibility of glioblastoma cells to NK cytotoxicity.

Indexed as

Gene Expression Regulation, NeoplasticBiomarkers, TumorBrain NeoplasmsCCAAT-Enhancer-Binding Protein-alphaCell Line, TumorCells, CulturedCystatinsCytotoxicity, ImmunologicGlioblastomaHumansImmunohistochemistryKiller Cells, NaturalMicrogliaMonocytesNeoplastic Stem CellsReverse Transcriptase Polymerase Chain ReactionBiomarkers, TumorCCAAT-Enhancer-Binding Protein-alphaCST7 protein, humanCystatinsCancer stem-like cellsCystatin FGlioblastomaImmunosuppressionNK cells

Identifiers

PMID34189679
PMCPMC12980675
OpenAlexW3174782477

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.