Evidence map›Paper›PMID 42033132›Full record

ArticleHead & neck2026

Cigarette Smoke Exposure Attenuates T2R-Mediated Apoptosis in Head and Neck Squamous Cell Carcinoma.

Kyle Polen, Sarah Sywanycz, Gavin Turner, Brianna L Hill, Lily Huang, Zoey A Miller, Casey Hanna, Lovely Raghav, Devraj Basu, Robert J Lee and 1 more

Abstract read
In one paragraph

Article in Head & neck, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Kyle PolenPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0009-0003-7775-111X
Sarah SywanyczDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Gavin TurnerPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Brianna L HillDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Lily HuangPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-3713-3443
Zoey A MillerDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Casey HannaDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Lovely RaghavDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Devraj BasuDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Robert J LeeDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
Ryan M CareyDepartment of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-0186-2265

Funding

Immune function of bitter taste receptors in human macrophagesR01AI167971 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Nithin Adappa, Robert J. Lee · 2022 to 2026
$2.5M
Exploiting differences in HPV oncoprotein function among oropharyngeal cancers to personalize therapyR01DE034056 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI Devraj Basu · 2024 to 2026
$1.7M
Intracellular signaling in airway solitary chemosensory (tuft) cellsR01HL168060 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Robert J. Lee · 2024 to 2026
$1.4M
Bitter taste receptors in oral cancer tumor-associated macrophagesR01DE034474 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI Ryan Michael Carey · 2025 to 2026
$1.0M
Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgeryUH2CA267502 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ · 2022 to 2023
$415k
NCI NIH HHS UH2 CA267502NHLBI NIH HHS R01 HL168060NIAID NIH HHS R01 AI167971NIDCR NIH HHS R01 DE034056NIDCR NIH HHS R01 DE034474NIH HHS AI167971NIH HHS DE034474NIH HHS HL168060
6 · The paper itself

Abstract

backgroundTobacco use is associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). Bitter taste receptor (T2R) activation induces apoptosis via calcium-dependent signaling, and higher T2R expression correlates with increased survival in HNSCC. However, the effects of cigarette smoke on T2R signaling remain unclear.

methodsHNSCC cell lines were treated with cigarette smoke condensate (CSC). T2R expression was measured by qPCR, and function evaluated by calcium imaging, viability, and apoptosis assays following stimulation with denatonium benzoate and flufenamic acid. T2R expression was also assessed in patient-derived tumor tissue and The Cancer Genome Atlas (TCGA).

resultsCSC reduced T2R expression, impaired calcium signaling, and diminished T2R-mediated apoptosis, particularly in SCC47 cells. Lower expression was observed in CSC-exposed patient-derived tumor tissue and TCGA tumors from smokers versus nonsmokers.

conclusionsCigarette smoke disrupts T2R signaling and reduces apoptosis in HNSCC, suggesting a mechanism by which ongoing tobacco use may alter tumor biology and treatment response.

Indexed as

ApoptosisCarcinoma, Squamous CellHead and Neck NeoplasmsReceptors, G-Protein-CoupledSmokeCalcium SignalingCell Line, TumorHumansSignal TransductionSmokingSquamous Cell Carcinoma of Head and NeckTaste Receptors, Type 2Receptors, G-Protein-CoupledSmokeTaste Receptors, Type 2apoptosisbitter taste receptors (T2Rs)calcium signalingcigarette smoke condensate (CSC)head and neck squamous cell carcinoma (HNSCC)

Identifiers

PMID42033132
PMCPMC13595459

What OpenQuestion holds

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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.