PXD081773-1

PXD081773 is an original dataset announced via ProteomeXchange.

Title	Targeting of CGRP signaling reverses maladaptive neurogenic immunosuppression in head and neck squamous cell carcinoma
Description	Neurogenic inflammation is one component that sculpts the immune milieu of solid tumors. However, it remains unclear how the sensory-neuroimmune axis shapes the immune microenvironment in cold tumors to bolster treatment resistance. Using orthotopic head and neck squamous cell carcinoma (HNSCC) models, we demonstrate that tumor growth-induced sensory hyperexcitability, and surgical sensory signaling interruption reduced tumor growth. Genetic knockout of a key neuropeptide released by sensory neurons, calcitonin gene-related peptide (CGRP), encoded by Calca, produced eradication when paired with multimodal radioimmunotherapy (RT + αPD1). Such treatment reduced Treg infiltration and immunosuppressive function in Calca knockout mice. We also observed that high-dose psilocybin functions as a CGRP inhibitor and transiently reduces tumor growth by increasing antitumor immunity. Additionally, psilocybin increased circulating serotonin, which was partially reversed with platelet activation inhibitor, clopidogrel. We observed differential effects on CD8 and Treg functionality by psilocin in vitro. Correlational analyses in plasma from human subjects following a single-dose psilocybin corroborated these findings. Together, this work underscores the complex interaction of neurogenic inflammation and the tumor immune microenvironment, highlighting potentially new therapeutic avenues for HNSCC and other solid tumors.
HostingRepository	PRIDE
AnnounceDate	2026-09-10
AnnouncementXML	Submission_2026-09-10_06:15:11.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Saviola
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-28 04:32:40	ID requested
⏵ 1	2026-09-10 06:15:11	announced

Dataset with its publication pending

submitter keyword: CGRP signaling,head and neck squamous cell carcinoma

Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.edu
lab head
Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD081773
     1. Label: PRIDE project
     2. Name: Targeting of CGRP signaling reverses maladaptive neurogenic immunosuppression in head and neck squamous cell carcinoma