Evidence map›Paper›PMID 36460334›Full record

ArticleJournal for immunotherapy of cancer2022

T cells of colorectal cancer patients' stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells.

Sandra Schwarz, Johanna Schmitz, Markus W Löffler, Michael Ghosh, Hans-Georg Rammensee, Evgenia Olshvang, Marvin Markel, Nadine Mockel-Tenbrinck, Andrzej Dzionek, Susann Krake and 7 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 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

17 authors at 6 institutions in 1 country.

Sandra SchwarzDepartment of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock, Germany.ORCID 0000-0002-8112-4392
Johanna SchmitzDepartment of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock, Germany.
Markus W LöfflerDepartment of General, Visceral and Transplant Surgery, Universitätsklinikum Tübingen, Tubingen, Germany.ORCID 0000-0003-2513-1317
Michael GhoshDepartment of Immunology, University of Tübingen, Tubingen, Germany.
Hans-Georg RammenseeDepartment of Immunology, University of Tübingen, Tubingen, Germany.ORCID 0000-0003-1614-2647
Evgenia OlshvangMiltenyi Biotec BV & Co KG, Bergisch Gladbach, Germany.
Marvin MarkelMiltenyi Biotec BV & Co KG, Bergisch Gladbach, Germany.
Nadine Mockel-TenbrinckMiltenyi Biotec BV & Co KG, Bergisch Gladbach, Germany.
Andrzej DzionekMiltenyi Biotec BV & Co KG, Bergisch Gladbach, Germany.
Susann KrakeCentogene GmbH, Rostock, Germany.
Basak ArslanCentogene GmbH, Rostock, Germany.
Kapil Dev KampeCentogene GmbH, Rostock, Germany.
Anne WendtCentogene GmbH, Rostock, Germany.
Peter BauerCentogene GmbH, Rostock, Germany.
Christina S MullinsDepartment of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock, Germany.
Andreas SchlosserCenter for Integrative and Translational Bioimaging, Rudolf-Virchow Center, University of Würzburg, Würzburg, Germany.
Michael LinnebacherDepartment of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock, Germany michael.linnebacher@med.uni-rostock.de.ORCID 0000-0001-8054-1402
Centogene (Germany) · DEMiltenyi Biotec (Germany) · DEUniversity of Rostock · DEGerman Cancer Research Center · DEUniversity of Tübingen · DEUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc).

methodsColorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients' Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay.

results100 tumor-specific candidate peptides-97 cryptic peptides and 3 classically mutated neoantigens-were selected. The neoantigens originated from single nucleotide substitutions in the genes

conclusionThese results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.

Indexed as

Colorectal NeoplasmsPeptidesAntigen-Presenting CellsEnzyme-Linked Immunospot AssayHumansLymphocyte CountTumor MicroenvironmentPeptidesAntigen PresentationAntigens, NeoplasmGastrointestinal NeoplasmsLymphocytes, Tumor-InfiltratingT-Lymphocytes

Identifiers

PMID36460334
PMCPMC9723954
OpenAlexW4310784434

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.