PXD048141

PXD048141 is an original dataset announced via ProteomeXchange.

Title	Golgi-ER Axis Regulates Anti-Tumor T Cell Immunotherapeutic Response
Description	The cumulative role of cellular organelle’s in shaping the life and function of a cell has been long acknowledged. While each organelle plays a specific role in the growth and development of T cells, numerous studies have thus far focused on targeting mitochondria, endoplasmic reticulum, or lysosome related pathways to improve anti-tumor T cell immune response. Here we highlight the tumor microenvironment (TME) mediated disruption of Golgi architecture and function, termed Golgi stress, contributes to altered redox signaling and affects cell survival. Importantly, the decreased expression if GM130, a marker of Golgi stress and indicating the disruption of Golgi architecture, was reverted upon treatment with hydrogen sulphide (H2S) donor GYY4137, or over expressing cystathionine β-synthase (Cbs), an enzyme involved in biosynthesis of endogenous H2S. Activation and expansion of tumor reactive TCR or chimeric antigen receptor bearing T cells expanded with exogenous H2S promoted stemness, antioxidant capacity and exhibited an increase effector cytokine secretion that correlated to increased protein translation. In in vivo models of melanoma and lymphoma, anti-tumor T cells conditioned ex vivo with exogenous H2S or overexpressing Cbs demonstrated superior tumor control upon ACT. Further, sorting anti-tumor T cells based on Golgi structure and abundance resulted in identification of a Golgihi subset of T cells with a unique metabolic signature, superior fitness, and enhanced anti-tumor capacity. These data suggest that H2S can be used an immunomodulatory agent to enhance the efficacy of ACT, and that the structure and function of the Golgi apparatus is an important feature of T cells that determines their anti-tumor capacity.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:50:40.949.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-27 04:12:49	ID requested
⏵ 1	2025-05-06 12:50:41	announced

10.1126/sciadv.adp1152;

Oberholtzer N, Chakraborty P, Kassir MF, Dressman J, Das S, Mills S, Comte-Walters S, Gooz M, Choi S, Parikh RY, Hedley Z, Vaena S, DeMass R, Scurti G, Romeo M, Gangaraju VK, Berto S, Hill E, Ball LE, Mehta AS, Maldonado EN, Nishimura MI, Ogretmen B, Mehrotra S, S-Prdx4 axis mitigates Golgi stress to bolster tumor-reactive T cell immunotherapeutic response. Sci Adv, 10(46):eadp1152(2024) [pubmed]

submitter keyword: T cell, Golgi apparatus, Immunotherapy

Shikhar Mehrotra
contact affiliation	Department of Surgery Hollings Cancer Center (HO 512H) Medical University of South Carolina
contact email	mehrotr@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.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/2025/05/PXD048141

PRIDE project URI

• PRIDE
  1. PXD048141
     1. Label: PRIDE project
     2. Name: Golgi-ER Axis Regulates Anti-Tumor T Cell Immunotherapeutic Response