PXD063865-1

PXD063865 is an original dataset announced via ProteomeXchange.

Title	Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function
Description	Tumors that contain tumor-infiltrating lymphocytes (TIL) with tissue-resident memory T cells (TRM) features are associated with better patient prognoses. While CD8+ T cells that target tumors often fail to restrain tumor growth due to progressive T cell exhaustion, pathogen-specific TRM survey tissues and sustain protective capacity for years. We identified protein homeostasis (proteostasis)-related E3 ubiquitin ligase genes shared by TRM and progenitor-exhausted TIL (TPEX), that are lost as TIL become terminally-exhausted (TEX). Sustained ligase expression led to increased TCF1+ T cell accumulation and improved anti-tumor function and less T cell exhaustion in chronic infection. Loss-of-function in cancer models impaired TIL accumulation and function and altered T cell differentiation in response to acute infection. Low-input mass spectrometry revealed abundant expression of protein degradation pathways by TEX, yet they accumulated unfolded proteins. Ligase overexpression rescued unfolded protein accumulation in TEX, demonstrating their functional contribution to proteostasis. Ligase overexpression in combination with immune checkpoint blockade led to improved survival from murine melanoma, demonstrating that the relationship between proteostasis and T cell differentiation opens up new avenues for cancer immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2026-04-21
AnnouncementXML	Submission_2026-04-21_14:57:06.580.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xuezhen Ge
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-12 18:36:53	ID requested
⏵ 1	2026-04-21 14:57:07	announced

Dataset with its publication pending

submitter keyword: cancer, tumor-infiltrating lymphocyte, CD8+ T cell, E3 ubiquitin ligase, immunotherapy, tumor,proteostasis

Eric J Bennett
contact affiliation	Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.
contact email	e1bennett@ucsd.edu
lab head
Xuezhen Ge
contact affiliation	University of California San Diego
contact email	x1ge@ucsd.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063865

PRIDE project URI

• PRIDE
  1. PXD063865
     1. Label: PRIDE project
     2. Name: Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function