CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition.
CD8
FoxP3
digital spatial transcriptomics
head and neck cancer
immunotherapy
tumor microenvironment
Journal
The Laryngoscope
ISSN: 1531-4995
Titre abrégé: Laryngoscope
Pays: United States
ID NLM: 8607378
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
15
08
2022
received:
09
05
2022
accepted:
18
08
2022
medline:
13
7
2023
pubmed:
21
9
2022
entrez:
20
9
2022
Statut:
ppublish
Résumé
To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin. Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response. A subset of samples was characterized for T-cell related signatures using digital spatial genomic profiling. Post-treatment analysis revealed a significant decrease in FoxP3+ CD and an increase in CD8+ CDs in the TAS between patients receiving durvalumab and metformin versus durvlaumab alone. Both treatment arms demonstrated significant post-treatment increases in ID. Although HPV+ and HPV- had similar immune cell CDs in the tumor microenvironment, HPV+ pre-treatment samples had 1.60 times greater ID compared with HPV- samples, trending toward significance (p = 0.05). At baseline, pathologic responders demonstrated a 1.16-fold greater CD8+ CDs in the LTE (p = 0.045) and 2.28-fold greater ID (p = 0.001) than non-responders. Digital spatial profiling revealed upregulation of FoxP3+ and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the TAS (p = 0.006, p = 0.026) in samples from pathologic responders. Analysis of CD8+ and FoxP3+ detected population differences according to HPV status, pathologic response, and treatment. Greater CD8+-FoxP3+ ID was associated with pathologic response. CD8+ and FoxP3+ T-cell distributions may be predictive of response to immune checkpoint inhibition. gov (Identifier NCT03618654). 3 Laryngoscope, 133:1875-1884, 2023.
Substances chimiques
CD274 protein, human
0
Metformin
9100L32L2N
Banques de données
ClinicalTrials.gov
['NCT03618654']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1875-1884Informations de copyright
© 2022 The American Laryngological, Rhinological and Otological Society, Inc.
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