PXD026447

PXD026447 is an original dataset announced via ProteomeXchange.

Title	PD-L1 overexpression, SWI/SNF complex Deregulation and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells
Description	The growing tumor avoids recognition and destruction by immune system. During continuous stimulation of tumor infiltrating lymphocytes (TILs) by tumor, TILs become functionally exhausted. Thus, they become unable to kill tumor cells and to produce some cytokines, and lose their ability to proliferate. It collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level on cell surface, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodeling complex subunits and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cells number. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell line overexpressing PD-L1 that suggested the existence of general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on PD-L1 promoter region indicated that the strong BRM recruitment in control CD4+ T cells is replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that such epi-drugs as EZH2 inhibitors may be used as immunomodulators in cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_08:55:21.127.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Agata Malinowska
SpeciesList	scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; L-methionine removal; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-03 02:43:11	ID requested
⏵ 1	2022-02-17 08:55:21	announced

Jancewicz I, Szarkowska J, Konopinski R, Stachowiak M, Swiatek M, Blachnio K, Kubala S, Oksinska P, Cwiek P, Rusetska N, Tupalska A, Zeber-Lubecka N, Grabowska E, Swiderska B, Malinowska A, Mikula M, Jagielska B, Walewski J, Siedlecki JA, Sarnowski TJ, Markowicz S, Sarnowska EA, T Cells. Cancers (Basel), 13(16):(2021) [pubmed]

submitter keyword: CD4+ effector T cells

T cell exhaustion

SWI/SNF complex

PD-1

PD-L1

PD-L1/PD-1 axis

Michal Dadlez
contact affiliation	Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
contact email	michald@ibb.waw.pl
lab head
Agata Malinowska
contact affiliation	IBB PAS
contact email	esme@ibb.waw.pl
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/2022/02/PXD026447

PRIDE project URI

• PRIDE
  1. PXD026447
     1. Label: PRIDE project
     2. Name: PD-L1 overexpression, SWI/SNF complex Deregulation and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells