Evidence map›Paper›PMID 37732732›Full record

ArticleeLife2023

Complementary CRISPR screen highlights the contrasting role of membrane-bound and soluble ICAM-1 in regulating antigen-specific tumor cell killing by cytotoxic T cells.

Ann-Kathrin Herzfeldt, Marta Puig Gamez, Eva Martin, Lukasz Miloslaw Boryn, Praveen Baskaran, Heinrich J Huber, Michael Schuler, John E Park, Lee Kim Swee

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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  7. SubvertingBiology · 2024
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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 2 institutions in 2 countries.

Ann-Kathrin HerzfeldtDepartment of Cancer Immunology and Immune Modulation, Boehringer Ingelheim, Biberach an der Riss, Germany.ORCID 0000-0002-7882-8284
Marta Puig GamezDepartment of Cancer Immunology and Immune Modulation, Boehringer Ingelheim, Biberach an der Riss, Germany.ORCID 0009-0006-6047-8200
Eva MartinDepartment of Drug Discovery Sciences, Boehringer Ingelheim, Biberach an der Riss, Germany.
Lukasz Miloslaw BorynArdigen SA, Kraków, Poland.ORCID 0000-0001-8091-1071
Praveen BaskaranDepartment of Global Computational Biology and Digital Sciences, Boehringer Ingelheim, Biberach an der Riss, Germany.ORCID 0000-0003-2275-3516
Heinrich J HuberDrug Discovery Sciences, Boehringer Ingelheim, Biberach an der Riss, Germany.ORCID 0000-0003-4454-2971
Michael SchulerDepartment of Drug Discovery Sciences, Boehringer Ingelheim, Biberach an der Riss, Germany.
John E ParkDepartment of Cancer Immunology and Immune Modulation, Boehringer Ingelheim, Biberach an der Riss, Germany.ORCID 0000-0002-5674-6026
Lee Kim SweeDepartment of Cancer Immunology and Immune Modulation, Boehringer Ingelheim, Biberach an der Riss, Germany.
Boehringer Ingelheim (India) · INBoehringer Ingelheim (Australia) · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytotoxic CD8 +T lymphocytes (CTLs) are key players of adaptive anti-tumor immunity based on their ability to specifically recognize and destroy tumor cells. Many cancer immunotherapies rely on unleashing CTL function. However, tumors can evade killing through strategies which are not yet fully elucidated. To provide deeper insight into tumor evasion mechanisms in an antigen-dependent manner, we established a human co-culture system composed of tumor and primary immune cells. Using this system, we systematically investigated intrinsic regulators of tumor resistance by conducting a complementary CRISPR screen approach. By harnessing CRISPR activation (CRISPRa) and CRISPR knockout (KO) technology in parallel, we investigated gene gain-of-function as well as loss-of-function across genes with annotated function in a colon carcinoma cell line. CRISPRa and CRISPR KO screens uncovered 187 and 704 hits, respectively, with 60 gene hits overlapping between both. These data confirmed the role of interferon-γ (IFN-γ), tumor necrosis factor α (TNF-α) and autophagy pathways and uncovered novel genes implicated in tumor resistance to killing. Notably, we discovered that

Indexed as

Colonic NeoplasmsT-Lymphocytes, CytotoxicCell DeathClustered Regularly Interspaced Short Palindromic RepeatsHumansIntercellular Adhesion Molecule-1Interferon-gammaTumor Necrosis Factor-alphaIntercellular Adhesion Molecule-1Interferon-gammaTumor Necrosis Factor-alphacancer biologycancer immunologyCRISPRa screenCRISPR KO screencytotoxic T cellsgeneticsgenomicshumanICAM-1ILKAPtumor cell killing

Identifiers

PMID37732732
PMCPMC10586807
OpenAlexW4386910605

What OpenQuestion holds

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LicenceCC BY
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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.