Evidence map›Paper›PMID 38423011›Full record

ArticleMed (New York, N.Y.)2024

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

Laurel B Darragh, Alexander Nguyen, Tiffany T Pham, Shaquia Idlett-Ali, Michael W Knitz, Jacob Gadwa, Sanjana Bukkapatnam, Sophia Corbo, Nicholas A Olimpo, Diemmy Nguyen and 17 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Med (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
15.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 39 citations in OpenAlex.

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  14. Neuro-tumor interactions in peripheral tumors.Cancer metastasis reviews · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 4 institutions in 2 countries.

Laurel B DarraghDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Alexander NguyenDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Tiffany T PhamDepartment of Otolaryngology - Head and Neck Surgery, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Shaquia Idlett-AliDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Michael W KnitzDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Jacob GadwaDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Sanjana BukkapatnamDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Sophia CorboDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Nicholas A OlimpoDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Diemmy NguyenDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Benjamin Van CourtDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Brooke NeupertDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Justin YuDepartment of Otolaryngology - Head and Neck Surgery, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Richard B RossDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Michaele CorbisieroDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Khalid N M AbdelazeemDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Radiation Biology Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Sean P MaroneyDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
David C GalindoDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Laith MukdadDepartment of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Anthony SaviolaDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Molishree JoshiDepartment of Pharmacology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Ruth WhiteDepartment of Medicine, Columbia University, New York, NY, USA.
Yazeed AlhiyariDepartment of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Von SamediDepartment of Pathology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Adrie Van BokhovenDepartment of Pathology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.
Maie St JohnDepartment of Head & Neck Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Sana D KaramDepartment of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA. Electronic address: sana.karam@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USUniversity of California, Los Angeles · USColumbia University · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8M
Treating recurrent HNSCC with radiation and dual TGF-Beta/PD-L1.P50CA261605 · NCI · UNIVERSITY OF COLORADO DENVER · PI JIMENO, ANTONIO, WANG, XIAO-JING · 2021 to 2025
$10.1M
Training in Translational Research of Lung, Head and Neck CancerT32CA174648 · NCI · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2013 to 2022
$4.2M
Tackling Treg mediated resistance to radiation and anti-PDL1 in HNSCCsR01DE028529 · NIDCR · WASHINGTON UNIVERSITY · PI SANA D KARAM · 2019 to 2026
$3.7M
Institutional Training in Otolaryngology ResearchT32DC012280 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI Yuri Agrawal, Sue C. Kinnamon · 2013 to 2026
$3.4M
Sexual dimorphism and the immuno-modulatory role of estrogen signaling in HNSCCR01CA284651 · NCI · WASHINGTON UNIVERSITY · PI SANA D KARAM · 2023 to 2026
$2.6M
Role of EphB4-ephrin-B2 interaction in regulating crosstalk between cancer cell and vascular tumor microenvironment in head and neck cancerR01DE028282 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2019 to 2023
$2.4M
Regulation of transendothelial migration of Tregs in irradiated HNSCCs by EphB4-ephrinB2 interactionF31DE029997 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI DARRAGH, LAUREL B · 2021 to 2023
$131k
NCI NIH HHS P30 CA046934NCI NIH HHS P50 CA261605NCI NIH HHS R01 CA284651NCI NIH HHS T32 CA174648NIDCD NIH HHS T32 DC012280NIDCR NIH HHS F31 DE029997NIDCR NIH HHS R01 DE028282NIDCR NIH HHS R01 DE028529NIDDK NIH HHS P30 DK116073
6 · The paper itself

Abstract

backgroundPerineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.

methodsWe used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.

findingsCalcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo.

conclusionsOur data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes.

funding1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

Indexed as

Calcitonin Gene-Related PeptideHead and Neck NeoplasmsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesHumansMiceSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentCalcitonin Gene-Related PeptidecancerCGRPdenervationHNSCCimmunotherapyPreclinical researchradiation therapysensory nervesTME

Identifiers

PMID38423011
PMCPMC10939743
OpenAlexW4392246507

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.