Evidence map›Paper›PMID 39049036›Full record

ArticleJournal of translational medicine2024

Spatial dynamics of tertiary lymphoid aggregates in head and neck cancer: insights into immunotherapy response.

Habib Sadeghirad, James Monkman, Chin Wee Tan, Ning Liu, Joseph Yunis, Meg L Donovan, Afshin Moradi, Niyati Jhaveri, Chris Perry, Mark N Adams and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. The Prognostic Significance of Tertiary Lymphoid Structures in Head and Neck Cancers: A Systematic Review and Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
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  6. Decoding the breast cancer microenvironment by spatial multi-omics: from architecture to clinical translation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  9. Spatial proteomics: technical evolution and applications in cancer research.Frontiers in cell and developmental biology · 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

15 authors.

Habib SadeghiradFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
James MonkmanFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Chin Wee TanFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Ning LiuBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC, 3052, Australia.
Joseph YunisFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Meg L DonovanFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Afshin MoradiFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Niyati JhaveriDiscovery Applications, Akoya Biosciences, The Spatial Biology Company, Marlborough, MA, USA.
Chris PerryThe Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Mark N AdamsCentre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
Ken O'ByrneThe Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Majid E WarkianiUniversity of Technology Sydney, NSW, Australia.
Rahul LadwaFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.
Brett G M HughesThe Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
Arutha KulasingheFrazer Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia. Arutha.kulasinghe@uq.edu.au.ORCID 0000-0003-3224-7350

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response.

methodsIn this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform.

resultsOur proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of 'hot tumor' phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes.

conclusionThe study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.

Indexed as

Head and Neck NeoplasmsImmunotherapyTertiary Lymphoid StructuresTumor MicroenvironmentFemaleHumansMaleMiddle AgedProteomicsSquamous Cell Carcinoma of Head and NeckTreatment Outcome

Identifiers

PMID39049036
PMCPMC11267849

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.