PXD014612

PXD014612 is an original dataset announced via ProteomeXchange.

Title	Abberant Cathepsin S Activity Modulates the Immune Microenvironment in Follicular Lymphoma
Description	Tumor cells can induce their own advantageous microenvironment. Here, we describe aberrant cathepsin S (CTSS) activity to modulate T-cell activation in follicular lymphoma (FL). In donor-derived FLs following bone marrow transplantation, we identified independent acquisition of CTSS mutations at Y132 in the donor´s and recipient's tumors. In a larger cohort, 6% of FL (20/312) harbored CTSS mutations, mostly Y132D, another 14% had CTSS amplification (40/280). Y132D leads to accelerated conversion from pro-CTSS to active CTSS and increased substrate cleavage, including CD74, which regulates MHC-II restricted antigen-presentation. In co-culture experiments, CTSS mutant lymphoma cells induced increased antigen-specific CD4+ T-cell activation. Moreover, antigen-processing was the top upregulated pathway in CTSS mutant primary FL biopsies. Thus, aberrant CTSS activity is a promising target in lymphoma.
HostingRepository	PRIDE
AnnounceDate	2021-01-07
AnnouncementXML	Submission_2021-01-07_00:12:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Ludwig
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-15 03:18:17	ID requested
⏵ 1	2021-01-07 00:12:16	announced

Bararia D, Hildebrand JA, Stolz S, Haebe S, Alig S, Trevisani CP, Osorio-Barrios F, Bartoschek MD, Mentz M, Pastore A, Gaitzsch E, Heide M, Jurinovic V, Rautter K, Gunawardana J, Sabdia MB, Szczepanowski M, Richter J, Klapper W, Louissaint A, Ludwig C, Bultmann S, Leonhardt H, Eustermann S, Hopfner KP, Hiddemann W, von Bergwelt-Baildon M, Steidl C, Kridel R, Tobin JWD, Gandhi MK, Weinstock DM, Schmidt-Supprian M, S, á, rosi MB, Rudelius M, Passerini V, Mautner J, Weigert O, Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma. Cell Rep, 31(5):107522(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Cysteine-protease, Follicular Lymphoma, Hematology, hotspot mutations, immune signaling

Christina Ludwig
contact affiliation	Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS) Technical University Munich Gregor-Mendel-Straße 4 85354 Freising GERMANY
contact email	tina.ludwig@tum.de
lab head
Christina Ludwig
contact affiliation	TU Munich
contact email	tina.ludwig@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014612
     1. Label: PRIDE project
     2. Name: Abberant Cathepsin S Activity Modulates the Immune Microenvironment in Follicular Lymphoma