PXD018079

PXD018079 is an original dataset announced via ProteomeXchange.

Title	IgA transcytosis and tumor antigen recognition govern anti-tumor immunity in ovarian cancer
Description	Although most ovarian cancers show prognostically relevant activated T-cell infiltrates, response rates to immune checkpoint inhibitors are very modest4. Memory B-cell and plasma cell infiltrates have been associated with better outcome in ovarian cancer, but the nature and functional relevance of these responses are controversial. Using 3 independent cohorts totaling 575 high-grade serous ovarian cancer (HGSOC) patients, we show that robust humoral responses are heavily dominated by the production of polyclonal IgA, which binds to Polymeric IgA Receptors universally expressed on ovarian cancer cells. Notably, all tertiary lymphoid structures identified in ~21% of HGSOCs contain IgA-producing oligoclonal B-cells. Strikingly, tumor Bcell-derived IgAs effectively target extracellular oncogenic drivers, whereas IgA transcytosis through malignant epithelial cells elicits transcriptional changes that antagonize the RAS pathway and that sensitize tumor cells to T-cell cytolytic killing, hindering malignant progression. Thus, tumor antigen-specific and antigen-independent IgA responses antagonize ovarian cancer growth by governing coordinated tumor cell, T-cell and B-cell responses. These findings provides a platform for the identification of novel targets spontaneously recognized by intratumoral B-cell-derived antibodies, and suggest that immunotherapies that augment B-cell responses may be more effective than T-cell-centric approaches, particularly for malignancies resistant to checkpoint inhibitors.
HostingRepository	PRIDE
AnnounceDate	2020-12-01
AnnouncementXML	Submission_2021-03-22_23:14:09.902.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018079
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-17 03:38:33	ID requested
1	2020-11-30 23:12:28	announced
⏵ 2	2021-03-22 23:14:10	announced	2021-03-23: Updated publication reference for PubMed record(s): 33536615.

Biswas S, Mandal G, Payne KK, Anadon CM, Gatenbee CD, Chaurio RA, Costich TL, Moran C, Harro CM, Rigolizzo KE, Mine JA, Trillo-Tinoco J, Sasamoto N, Terry KL, Marchion D, Buras A, Wenham RM, Yu X, Townsend MK, Tworoger SS, Rodriguez PC, Anderson AR, Conejo-Garcia JR, IgA transcytosis and antigen recognition govern ovarian cancer immunity. Nature, 591(7850):464-470(2021) [pubmed]

submitter keyword: Ovarian Cancer, Immunoglobulin A, Transcytosis, LC-MS/MS, PRM, Immunotherapy

Jose Conejo-Garcia, MD/PhD
contact affiliation	Immunology, Moffitt Cancer Center, Tampa, FL
contact email	jose.conejo-garcia@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
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/2020/12/PXD018079

PRIDE project URI

• PRIDE
  1. PXD018079
     1. Label: PRIDE project
     2. Name: IgA transcytosis and tumor antigen recognition govern anti-tumor immunity in ovarian cancer