Evidence map›Paper›PMID 39963988›Full record

ArticleOncoimmunology2025

Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma.

Daniel A Ruiz-Torres, Michael E Bryan, Shun Hirayama, Ross D Merkin, Evelyn Luciani, Thomas J Roberts, Manisha Patel, Jong C Park, Lori J Wirth, Peter M Sadow and 3 more

Abstract read
In one paragraph

Article in Oncoimmunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 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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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

13 authors.

Daniel A Ruiz-TorresDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.
Michael E BryanDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.
Shun HirayamaDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.
Ross D MerkinDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Evelyn LucianiKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Thomas J RobertsDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Manisha PatelDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Jong C ParkDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Lori J WirthDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Peter M SadowDepartment of Medicine, Harvard Medical School, Boston MA, USA.
Moshe Sade-FeldmanKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Shannon L StottKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Daniel L FadenDepartment of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.

Funding

Benchmarking the Sensitivity and Specificity of the Herringbone Microfluidic Device for Rare Particle CaptureR01CA226871 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NAHED, BRIAN VALA, STOTT, SHANNON L · 2018 to 2023
$2.3M
Microfluidic Isolation and Characterization of SARS-CoV-2 and Virus Related ExosomesU18TR003793 · NCATS · MASSACHUSETTS GENERAL HOSPITAL · PI BOLAND, GENEVIEVE MARIE, STOTT, SHANNON L · 2021 to 2022
$2.0M
Dissecting temporal and spatial dynamics of immunotherapy resistanceK23DE029811 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2021 to 2025
$869k
Precision imaging of the spatial regulators of the hybrid epithelial/mesenchymal state in head and neck cancerR01DE033741 · NIDCR · MASSACHUSETTS GENERAL HOSPITAL · PI STOTT, SHANNON L · 2024 to 2024
$702k
Circulating HPV DNA as a Prediagnostic Marker of Oropharyngeal CancerR21CA267152 · NCI · UNIVERSITY OF KENTUCKY · PI FADEN, DANIEL, KUHS, KRYSTLE A. · 2022 to 2023
$431k
Cell free HPV DNA detection in the diagnostic and surgical settingsR03DE030550 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2022 to 2023
$336k
NCATS NIH HHS U18 TR003793NCI NIH HHS R01 CA226871NCI NIH HHS R21 CA267152NIDCR NIH HHS K23 DE029811NIDCR NIH HHS R01 DE033741NIDCR NIH HHS R03 DE030550
6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The combined positive score (CPS) for PD-L1 is the only biomarker approved to predict response to ICB and has limited performance. Tertiary Lymphoid Structures (TLS) have shown promising potential for predicting response to ICB. However, their exact composition, size, and spatial biology in HNSCC remain understudied. To elucidate the impact of TLS spatial biology in response to ICB, we utilized pre-ICB tumor tissue sections from 9 responders (complete response, partial response, or stable disease) and 11 non-responders (progressive disease) classified via RECISTv1.1. A custom multi-immunofluorescence (mIF) staining assay was applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblasts (α Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). A machine learning model was employed to measure the effect of spatial metrics on achieving a response to ICB. A higher density of B cells (CD20+) was found in responders compared to non-responders to ICB (

Indexed as

Biomarkers, TumorHead and Neck NeoplasmsImmune Checkpoint InhibitorsSquamous Cell Carcinoma of Head and NeckTertiary Lymphoid StructuresAgedFemaleHumansMaleMiddle AgedTumor MicroenvironmentBiomarkers, TumorImmune Checkpoint InhibitorsHead and neck cancerimmune checkpoint blockadespatial biologytertiary lymphoid structures

Identifiers

PMID39963988
PMCPMC11845054

What OpenQuestion holds

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Read underepoch 390

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.