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

作者：Habib Sadeghirad, James H. Monkman, Chin Wee Tan, Ning Liu, Joseph Yunis, Meg L. Donovan, Afshin Moradi, Niyati Jhaveri, Chris Perry, Mark N. Adams, Kenneth John O'Byrne, Majid Ebrahimi Warkiani, Rahul Ladwa, Brett G.M. Hughes, Arutha Kulasinghe · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05409-y · 被引用次数：34 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

BACKGROUND: Recurrent/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. METHODS: In 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. RESULTS: Our 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 upregula...