Evidence map›Paper›PMID 38702144›Full record

ArticleJournal for immunotherapy of cancer2024

CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model.

Jiyoung Yun, Robert Saddawi-Konefka, Benjamin Goldenson, Riyam Al-Msari, Davide Bernareggi, Jaya L Thangaraj, Shiqi Tang, Sonam H Patel, Sarah M Luna, J Silvio Gutkind and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

11 authors.

Jiyoung YunMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.ORCID http://orcid.org/0009-0004-4513-0201
Robert Saddawi-KonefkaMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.ORCID http://orcid.org/0000-0002-9936-1695
Benjamin GoldensonMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
Riyam Al-MsariMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
Davide BernareggiDept. of Medicine, University of California-San Diego, La Jolla, California, USA.
Jaya L ThangarajDept. of Medicine, University of California-San Diego, La Jolla, California, USA.
Shiqi TangMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
Sonam H PatelMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
Sarah M LunaMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
J Silvio GutkindMoores Cancer Center, University of California-San Diego, La Jolla, California, USA.
Dan KaufmanMoores Cancer Center, University of California-San Diego, La Jolla, California, USA dskaufman@ucsd.edu.ORCID http://orcid.org/0000-0002-2003-2494

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
A Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic StatesU01CA217885 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COHEN, EZRA, KAUFMAN, DAN S. · 2017 to 2021
$5.1M
Stimulating Neo-Antigen Specific T Cell Responses in Head and Neck CancersU01DE028227 · NIDCR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI GUTKIND, JORGE SILVIO, RAO, ANJANA · 2018 to 2022
$4.6M
Co-targeting the HER3 oncogenic signaling circuitry and PD-1 as a novel multimodal precision immunotherapy for HNSCCR01CA247551 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUTKIND, JORGE SILVIO · 2020 to 2024
$2.5M
Exploiting the HER3-PI3K/mTOR-Immune Axis to Design Precision Immune Oncology Therapy for Head & Neck CancerF32DE029990 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SADDAWI-KONEFKA, ROBERT · 2020 to 2020
$72k
NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA247551NCI NIH HHS U01 CA217885NIDCR NIH HHS F32 DE029990NIDCR NIH HHS U01 DE028227
6 · The paper itself

Abstract

backgroundNatural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A (

methodsHere, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts.

resultsWe found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4

conclusionsTogether, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.

Indexed as

Disease Models, AnimalHead and Neck NeoplasmsKiller Cells, NaturalSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorEndosomal Sorting Complexes Required for TransportHumansImmunocompetenceMiceChmp2a protein, mouseEndosomal Sorting Complexes Required for TransportImmunity, InnateImmunotherapyImmunotherapy, AdoptiveKiller Cells, NaturalMyeloid-Derived Suppressor Cells

Identifiers

PMID38702144
PMCPMC11086353

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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.