Evidence map›Paper›PMID 41923630›Full record

ArticleCell reports. Medicine2026

Single-cell analysis highlights the significance of malignant cell IFN/MHC-II for immunotherapy response in head and neck squamous cell carcinoma.

Michael Mints, Reilly A Sample, Anuraag S Parikh, Jesse M Zaretsky, Zongtai Qi, Travis Law, Fudong Wang, Thomas F Barrett, Riley Mullins, Ashley Reeb and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

27 authors.

Michael MintsDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Reilly A SampleDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Anuraag S ParikhDepartment of Otolaryngology-Head and Neck Surgery, Columbia University Irving Medical Center, New York, NY, USA.
Jesse M ZaretskyDepartment of Medicine/Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Zongtai QiDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Travis LawDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Fudong WangDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Thomas F BarrettDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Riley MullinsDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Ashley ReebDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Alissa C GreenwaldDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Emily StollerDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; University of Massachusetts Chan Medical School, Worcester, MA, USA.
Salma RamadanDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Sophie GerndtDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Peter OppeltDepartment of Medicine/Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Jessica LeyDepartment of Medicine/Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Wade ThorstadThe Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Randal C PanielloDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Jason T RichDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Richard A HarbisonDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Paul A ZolkindDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Ryan S JacksonDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Patrik PipkornDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Douglas R AdkinsDepartment of Medicine/Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA.
Ravindra UppaluriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Surgery/Otolaryngology, Brigham and Women's Hospital, Boston, MA, USA.
Itay TiroshDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: itay.tirosh@weizmann.ac.il.
Sidharth V PuramDepartment of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; The Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center at Siteman, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: sidpuram@wustl.edu.

Funding

3D Culture Models of Partial-EMT and Its Regulation in Oral Cavity Squamous Cell CarcinomaK08DE033093 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PARIKH, ANURAAG SUHRID · 2023 to 2025
$827k
NIDCR NIH HHS K08 DE033093
6 · The paper itself

Abstract

In head and neck squamous cell carcinoma (HNSCC), immunotherapy response rates remain modest, with difficulty predicting responders. Previous studies characterizing immunotherapy-associated cellular changes in HNSCC focus on immune cells, providing limited insight into malignant cell responses. Here, we perform single-cell RNA sequencing (RNA-seq) on 16 HNSCC patients pre- and post-neoadjuvant pembrolizumab treatment. We identify an interferon (IFN)/major histocompatibility complex class II (MHC-II) expression program in malignant cells, characterized by MHC-II and IFN-response genes, which is associated with response to pembrolizumab. We validate malignant cell MHC-II expression at the protein level via multiplexed immunofluorescence. In a murine HNSCC model, IFN-γ-induced malignant cell MHC-II expression marks immunotherapy-sensitive tumors with favorable immune microenvironments. Finally, we confirm that pre-treatment malignant-IFN/MHC-II is a marker of response through deconvolution of bulk RNA-seq data from an independent cohort. Beyond identifying the malignant IFN/MHC-II program as a potential biomarker for immunotherapy response in HNSCC, our work elucidates the important role of malignant cells in immunotherapy.

Indexed as

Head and Neck NeoplasmsHistocompatibility Antigens Class IIImmunotherapyInterferonsSingle-Cell AnalysisSquamous Cell Carcinoma of Head and NeckAnimalsAntibodies, Monoclonal, HumanizedFemaleGene Expression Regulation, NeoplasticHumansInterferon-gammaMaleMiceTumor MicroenvironmentAntibodies, Monoclonal, HumanizedHistocompatibility Antigens Class IIInterferon-gammaInterferonspembrolizumabsingle cell RNA-seq, immunotherapy, pembrolizumab, MHC-II, deconvolution, malignant cell biomarker

Identifiers

PMID41923630
PMCPMC13130666

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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.