PXD067046

PXD067046 is an original dataset announced via ProteomeXchange.

Title	Alprazolam abrogates TLR4 signaling and reduces inflammatory cytokine production in pancreatic cancer-associated fibroblasts
Description	Pancreatic ductal adenocarcinoma (PDAC) diagnoses are often accompanied by a number of physical and psychological symptoms, including anxiety and depression. As a result, many patients are prescribed anxiolytics such as benzodiazepines that have unintended effects on the tumor. Previous work from our lab has highlighted that structural differences between benzodiazepine compounds may be responsible for different clinical outcomes influenced by their effects on cancer-associated fibroblasts (CAFs) within the PDAC tumor microenvironment (TME). Here, we demonstrate that the commonly prescribed N-substituted triazolobenzodiazepine alprazolam (ALP) abrogates the production of proinflammatory cytokines including CCL2, CXCL12, IL6, and IL8 in human CAFs. This phenotype is unique only to azole-containing benzodiazepines, including midazolam. The ability of ALP to regulate proinflammatory cytokine production is maintained in vivo, as ALP-treated mice bearing pancreatic tumors exhibited reductions in IL6 within the tumor interstitial fluid. Mechanistically, an unbiased phosphoproteomic approach revealed that ALP abrogates TLR4-mediated cytokine production in CAFs. These findings cumulatively support that ALP dampens CAF-mediated inflammatory signaling within the PDAC TME.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:13:34.599.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD067046
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Amanda Smythers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-07 05:32:32	ID requested
⏵ 1	2026-06-07 16:13:35	announced

10.1158/2767-9764.crc-25-0472;

Reavis HD, Chaubey AH, Smythers AL, Tisdale AA, Tracz A, Dimeck AN, Maraszek KE, Cortes Gomez E, Paulo JA, Dasgupta S, Gygi SP, Feigin ME, Alprazolam Reduces Inflammatory Cytokine Production in Pancreatic Cancer-Associated Fibroblasts. Cancer Res Commun, 6(5):1048-1060(2026) [pubmed]

10.6019/PXD067046;

submitter keyword: pancreatic cancer, TMT, phosphoproteomics

Amanda Smythers
contact affiliation	Dana-Farber Cancer Institute
contact email	amanda_smythers@dfci.harvard.edu
lab head
Amanda Smythers
contact affiliation	Dana Farber Cancer Institute, Harvard Medical School
contact email	amanda_smythers@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067046
     1. Label: PRIDE project
     2. Name: Alprazolam abrogates TLR4 signaling and reduces inflammatory cytokine production in pancreatic cancer-associated fibroblasts