Spatial resolution of the head and neck cancer tumor microenvironment to identify tumor and stromal features associated with therapy response.
Head and neck cancer
immunotherapy
spatial profiling
spatial proteomics
whole‐transcriptome analyses
Journal
Immunology and cell biology
ISSN: 1440-1711
Titre abrégé: Immunol Cell Biol
Pays: United States
ID NLM: 8706300
Informations de publication
Date de publication:
24 Jul 2024
24 Jul 2024
Historique:
revised:
29
05
2024
revised:
30
06
2024
received:
20
02
2024
accepted:
05
07
2024
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
24
7
2024
Statut:
aheadofprint
Résumé
Head and neck cancer (HNC) is the seventh most common cancer globally, resulting in 440 000 deaths per year. While there have been advancements in chemoradiotherapy and surgery, relapse occurs in more than half of HNCs, and these patients have a median survival of 10 months and a 2-year survival of < 20%. Only a subset of patients displays durable benefits from immunotherapies in metastatic and recurrent HNC, making it critical to understand the tumor microenvironment (TME) underpinning therapy responses in HNC. To recognize biological differences within the TME that may be predictive of immunotherapy response, we applied cutting-edge geospatial whole-transcriptome profiling (NanoString GeoMx Digital Spatial Profiler) and spatial proteomics profiling (Akoya PhenoCycler-Fusion) on a tumor microarray consisting of 25 cores from 12 patients that included 4 immunotherapy-unresponsive (8 cores) and 2 immunotherapy-responsive patients (5 cores), as well as 6 immunotherapy naïve patients (12 cores). Through high-plex, regional-based transcriptomic mapping of the tumor and TME, pathways involved with the complement system and hypoxia were identified to be differentially expressed in patients who went on to experience a poor immunotherapy response. Single-cell, targeted proteomic analysis found that immune cell infiltration of the cancer cell mass and interactions of CD8 T cells with tumor and other immune cells were associated with positive immunotherapy response. The relative abundance of specific tumor phenotypes and their interactions with various immune cells was identified to be different between response groups. This study demonstrates how spatial transcriptomics and proteomics can resolve novel alterations in the TME of HNC that may contribute to therapy sensitivity and resistance.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : PA Research Foundation (PARF)
Informations de copyright
© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.
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