PXD049402-1

PXD049402 is an original dataset announced via ProteomeXchange.

Title	A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity
Description	CRISPR screens in CD8+ T cells have uncovered novel immunotherapy targets for cancer; however, these screens used activated CD8+ T cells, precluding identification of genes regulating CD8+ T cell priming in the tumor-draining lymph (tdLN). Here we present an 899-gene in vivo CRISPR screen in naive CD8+ T cells, which identifies novel regulators of CD8+ T cell responses in the tdLN and tumor. We find that STUB1, an E3 ubiquitin ligase, significantly regulates CD8+ T cell accumulation in both tissues and Stub1 knockout (KO) CD8+ T cells improve tumor growth control. Mechanistically, STUB1 interacts with the adapter protein, CHIC2, to regulate IL-27Rα, which is required for the increased anti-tumor responses of Stub1 and Chic2 KO CD8+ T cells. Overall, these findings demonstrate that the STUB1-CHIC2 complex is a novel regulator of cytokine receptor expression in CD8+ T cells and provide the rationale for inhibiting this pathway to improve CD8+ T cell-mediated anti-tumor immunity.
HostingRepository	PRIDE
AnnounceDate	2025-08-12
AnnouncementXML	Submission_2025-08-12_10:52:02.799.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin LaFleur
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-15 06:42:08	ID requested
⏵ 1	2025-08-12 10:52:03	announced

10.1038/S41590-025-02231-6;

submitter keyword: Tumor immunity, IL27Ra, CRISPR,Stub1, Chic2

Arlene Helen Sharpe
contact affiliation	Department of Immunology, Harvard Medical School, U.S.A.
contact email	arlene_sharpe@hms.harvard.edu
lab head
Martin LaFleur
contact affiliation	Harvard Medical School
contact email	martin_lafleur@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049402
     1. Label: PRIDE project
     2. Name: A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity