PXD027240

PXD027240 is an original dataset announced via ProteomeXchange.

Title	proteomic profiling of small extracellular vesicles (EVs), released by chronic myeloid leukemia cells K562
Description	Chronic and acute myeloid leukemia (CML/AML) evade immune surveillance and induce immunosuppression, largely by upregulating Foxp3+ regulatory T cells (Treg). However, mechanisms that drive Treg in myeloid leukemias are largely unknown. Here, we show that leukemic (CML- and AML-derived) extracellular vesicles (EVs) drive human Treg, by de novo induction of Treg and by upregulating suppressive phenotype and activity of Treg. Rab27a-mediated EVs secretion contributed to Treg expansion, activity, and leukemic engraftment in vivo in a mouse model of CML-like disease. Leukemic EVs downregulated mTOR-S6 and upregulated STAT5 signaling in T cells, to upregulate Foxp3 and Treg activity, as well as evoked significant transcriptomic changes in Treg. By using high resolution 23-color spectral flow cytometry we identified 2 distinct, highly suppressive subsets of Treg expanded by leukemic EVs, characterized by elevated expression of tumor Treg markers CCR8, CCR4, TIGIT, CD39, CD30, TNFR2 and IL21R. Finally, we identified 4 1BBL/TNFSF9 protein in leukemic EVs. Deficiency of 4-1BBL in leukemic cells and EVs resulted in lower expression of CD30, TNFR2 and LAG-3 on Treg and thus weaker effector phenotype. Collectively, our data pinpoint leukemic extracellular vesicles as a significant factor that drives regulatory T cells and immunosuppression in myeloid leukemias. Our results suggest that targeting of Rab27a and EVs secretion may be a viable therapeutic option in myeloid leukemias, whereas detection of 4 1BBL containing EVs could be used as an early biomarker of immunosuppression and leukemia development/relapse
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:15.759.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominik Cysewski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-12 01:43:21	ID requested
1	2022-02-16 05:40:28	announced
⏵ 2	2023-11-14 08:53:16	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: leukemia,K562, extracelluar vesicles, EVs

Katarzyna Piwocka
contact affiliation	Nencki Institute of Experimental Biology Polish Academy of Sciences 3 Pasteur Str. 02-093 Warsaw, Poland
contact email	k.piwocka@nencki.edu.pl
lab head
Dominik Cysewski
contact affiliation	Medical University of Bialystok
contact email	dominikcysewski@gmail.com
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/PXD027240

PRIDE project URI

• PRIDE
  1. PXD027240
     1. Label: PRIDE project
     2. Name: proteomic profiling of small extracellular vesicles (EVs), released by chronic myeloid leukemia cells K562