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- Title
CD8+ and FoxP3+ T‐Cell Cellular Density and Spatial Distribution After Programmed Death‐Ligand 1 Check Point Inhibition.
- Authors
Curry, Joseph; Alnemri, Angela; Philips, Ramez; Fiorella, Michele; Sussman, Sarah; Stapp, Robert; Solomides, Charalambos; Harshyne, Larry; South, Andrew; Luginbuhl, Adam; Tuluc, Madalina; Martinez‐Outschoorn, Ubaldo; Argiris, Athanassios; Linnenbach, Alban; Johnson, Jennifer
- Abstract
Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. ClinicalTrials.gov (Identifier NCT03618654). Level of Evidence: 3 Laryngoscope, 133:1875–1884, 2023
- Subjects
CHECK Point Software Technologies Ltd.; PROGRAMMED death-ligand 1; CD8 antigen; IMMUNE checkpoint inhibitors; PROGRAMMED cell death 1 receptors; T cells; DIGITAL signatures
- Publication
Laryngoscope, 2023, Vol 133, Issue 8, p1875
- ISSN
0023-852X
- Publication type
Article
- DOI
10.1002/lary.30389