Evidence map›Paper›PMID 38493204›Full record

ArticleScientific reports2024

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.

Takahide Nejo, Lin Wang, Kevin K Leung, Albert Wang, Senthilnath Lakshmanachetty, Marco Gallus, Darwin W Kwok, Chibo Hong, Lee H Chen, Diego A Carrera and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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  11. Engineered Antibodies as Cancer Radiotheranostics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 1 country.

Takahide NejoDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Lin WangDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Albert WangDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Senthilnath LakshmanachettyDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Marco GallusDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Darwin W KwokDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Chibo HongDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Lee H ChenDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Diego A CarreraDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Michael Y ZhangDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Nicholas O SteversDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Gabriella C MaldonadoDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Akane YamamichiDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Payal B WatchmakerDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Akul NaikDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Anny ShaiDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Susan M ChangDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Arun P WiitaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Joseph F CostelloDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Aaron A DiazDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA.
Hideho OkadaDepartment of Neurological Surgery, University of California, San Francisco (UCSF), 1450 3Rd Street, Box 0520, San Francisco, CA, 94158, USA. hideho.okada@ucsf.edu.
University of California, San Francisco · USNeurological Surgery · USParker Institute for Cancer Immunotherapy · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Preclinical development of breakthrough immunotherapy for brain tumorsR35NS105068 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2018 to 2025
$6.0M
3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformationR01CA244838 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2020 to 2024
$2.7M
An informatics framework for single-cell multi-omics from clinical specimensR01LM013897 · NLM · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aaron Antonio Diaz · 2022 to 2026
$1.8M
The Immortality and Evolution of Adult Brain TumorsR50CA274229 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Chibo Hong · 2022 to 2026
$899k
NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA244838NCI NIH HHS R50 CA274229NCI NIH HHS T32 CA151022NIH HHS 1R35 NS105068NIH HHS R50CA274229NINDS NIH HHS R35 NS105068NLM NIH HHS R01 LM013897
6 · The paper itself

Abstract

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

Indexed as

GlioblastomaGliomaAlternative SplicingAntigens, NeoplasmAntigens, SurfaceHistocompatibility AntigensHumansReceptor-Like Protein Tyrosine Phosphatases, Class 5RNAAntigens, NeoplasmAntigens, SurfaceHistocompatibility AntigensPTPRZ1 protein, humanReceptor-Like Protein Tyrosine Phosphatases, Class 5RNAAlternative splicingAntigenBulk RNA-sequencingGliomaIntratumoral heterogeneityLong-read sequencingNeojunctionProteomics

Identifiers

PMID38493204
PMCPMC10944514
OpenAlexW4392882159

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Registered trials

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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.