ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Immunostimulatory Cancer-Associated Fibroblast Subpopulations Can Predict Immunotherapy Response in Head and Neck Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Three-Year Follow-Up of Neoadjuvant Tislelizumab with Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Revealing Cancer-Associated Fibroblast Heterogeneity Corresponding to PD-1 Blockade Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Trial
- Immune-featured stromal niches associate with response to neoadjuvant immunotherapy in oral squamous cell carcinoma.Cell reports. Medicine · 2025Trial
- Photodynamic therapy in head and neck squamous cell carcinoma: immunomodulation and stromal targeting of cancer-associated fibroblasts.Translational oncology · 2026Review
- Review
- ZC3H13-mediated m6A stabilization of CCND1 promotes malignant progression and is associated with poor anti-PD-1 response in HNSCC.Clinical and translational medicine · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Review
- Driving progress in recurrent and metastatic head and neck cancer: the NRG Oncology perspective.Journal of the National Cancer Institute · 2026Review
- Molecular and Immune Landscape of Recurrent and/or Distant Metastatic Squamous Cell Carcinoma of the Head and Neck: An EORTC/IMMUCAN Project.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Challenges in tracer development for tumor microenvironment (TME) imaging.European journal of nuclear medicine and molecular imaging · 2026Review
- Patient-specific lung cancer tumoroids recapitulate the tumor microenvironments for functional evaluation of therapeutic responses and immune-stromal interactions.Journal of translational medicine · 2026Article
- Glycolytic cancer-associated fibroblasts orchestrate metabolic remodeling in the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2026Review
- Pan-cancer single-cell and spatial transcriptomics analyses delineate response-associated heterogeneity and therapeutic targets of tumor-infiltrating B cells following immune checkpoint blockade.Cancer immunology, immunotherapy : CII · 2026Article
- ICIsAtlas reveals a suppressive NK cell niche in pan-cancer immunotherapy profiles.Communications biology · 2026Article
- Review
- Loss of Gαq reshapes fibroblast traits and drives tumor-stroma remodeling in oral cancer progression.EMBO reports · 2026Article
- A Head and Neck Cancer Patient-Specific Microphysiological System for Predicting Response to Chemoradiation.bioRxiv : the preprint server for biology · 2026Article
- Integrative immune subtyping of HNSCC reveals clinically relevant phenotypes and treatment-associated transitions.NPJ precision oncology · 2026Article
- Genomic and Immune Landscape of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Progressing on Anti-PD-1 Treatment.Cancer immunology research · 2026Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
purposeCancer-associated fibroblasts (CAF) have been implicated as potential mediators of checkpoint immunotherapy response. However, the extensive heterogeneity of these cells has precluded rigorous understanding of their immunoregulatory role in the tumor microenvironment. EXPERIMENTAL
designWe performed high-dimensional single-cell RNA sequencing (scRNA-seq) on four patient tumors pretreatment and posttreatment from a neoadjuvant trial of patients with advanced-stage head and neck squamous cell carcinoma that were treated with the αPD-1 therapy, nivolumab. The head and neck CAF (HNCAF) protein activity profiles, derived from this cohort of paired scRNA-seq, were used to perform protein activity enrichment analysis on the 28-patient parental cohort of clinically annotated bulk transcriptomic profiles. Ex vivo coculture assays were used to test functional relevance of HNCAF subtypes.
resultsFourteen distinct cell types were identified with the fibroblast population showing significant changes in abundance following nivolumab treatment. Among the fibroblast subtypes, HNCAF-0/3 emerged as predictive of nivolumab response, while HNCAF-1 was associated with immunosuppression. Functionally, HNCAF-0/3 were found to reduce TGFβ-dependent PD-1+TIM-3+ exhaustion of CD8 T cells, increase CD103+NKG2A+ resident memory phenotypes, and enhance the overall cytolytic profile of T cells.
conclusionsOur findings demonstrate the functional importance of distinct HNCAF subsets in modulating the immunoregulatory milieu of human HNSCC. In addition, we have identified clinically actionable HNCAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.
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Registered trials
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.