PXD055262 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | BTN2A1 Targeting Reprograms M2-like Macrophages and TAMs via SYK and MAPK Signaling |
Description | Tumor-associated macrophages (TAMs), often adopting an immunosuppressive M2-like phenotype, correlate with unfavorable cancer outcomes. Our investigation unveiled elevated expression of the butyrophilin (BTN)2A1 in M2-like TAMs across diverse cancer types. We developed anti-BTN2A1 monoclonal antibodies (mAb) and notably, one clone demonstrated a robust inhibitory effect on M2-like macrophage differentiation, inducing a shift towards an M1-like phenotype both in vitro and ex vivo in TAMs from patients with cancer. Macrophages treated with this anti-BTN2A1 mAb exhibited enhanced support for T-cell proliferation and IFNγ secretion. Indeed, M1-like and M2-like macrophage differentiation involves complex signaling pathways leading to specific gene expression profiles. Typically, stimuli from the TME induce pathways including JAK/STATs, MAPK, PI3K/AKT, NOTCH and NF-κB influencing TAMs polarization. We investigated the signaling pathways activated in monocytes and M-CSF-induced M2-like macrophages upon BTN2A1 engagement using anti-BTN2A mAb5. After 30 min of treatment, we observed phosphorylation of MAPKs (i.e. ERK1/2, P38 and JNK) in CD14+ monocytes and in M2-like macrophages, unlike isotype control-treated cells. In contrast, the PI3K/AKT, JAK/STAT, and NF-kB pathways were not consistently activated after 30 min of anti-BTN2A mAb5 treatment. Since BTN2A1 lacks intrinsic kinase activity, we explored whether BTN2A1 could form complexes with molecular partners in M2-like macrophages that provide kinase activity. We prepared lysates from M2-like macrophages treated with mAb5 or with its isotype control for 30 min and performed immunoprecipitation (IP) using another anti-BTN2A mAb followed by western blotting with anti-phosphoTyrosine (pTyr). A 70 kDa was co-immunoprecipitated with BTN2A1 and revealed by the anti-pTyr in lysates from anti-BTN2A mAb5-treated M2-like macrophages. To identify which Tyrosine kinase is enriched in anti-BTN2A mAb5-treated M2-like macrophages, we performed LC-MS/MS on anti-pTyr immunoprecipitates from treated cells. Several tyrosine kinases, including P38α/δ and JNK, were enriched. Notably, SYK was also identified and matched the 72kDa molecular weight of the pTyr band co-immunoprecipitated with BTN2A1. |
HostingRepository | PRIDE |
AnnounceDate | 2024-09-02 |
AnnouncementXML | Submission_2024-09-02_06:47:18.604.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | AUDEBERT Stephane |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-08-27 12:17:19 | ID requested | |
⏵ 1 | 2024-09-02 06:47:19 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LC-MSMS, AP-MS, Butyrophilin (BTN)2A1, Reprogramming, MAPK, Immunosuppressive M2-like, SYK,Cancer |
Contact List
OLIVE Daniel, PU-PH, |
contact affiliation | Centre de Recherche en Cancérologie de Marseille, CRCM Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France |
contact email | Daniel.Olive@inserm.fr |
lab head | |
AUDEBERT Stephane |
contact affiliation | Marseille Proteomic, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France |
contact email | stephane.audebert@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD055262
- Label: PRIDE project
- Name: BTN2A1 Targeting Reprograms M2-like Macrophages and TAMs via SYK and MAPK Signaling