Association between spatial distribution of leukocyte subsets and clinical presentation of head and neck squamous cell carcinoma

Le résumé fourni par la source

Background Development and metastasis of head and neck squamous cell carcinoma (HNSCC) involve complex interactions between tumor cells and the microenvironment. Spatial cell arrangement significantly influences these interactions. Methods The spatial distribution of leukocyte subsets in HNSCC was analyzed by multiplex immunohistochemistry (IHC) and correlated with clinical outcome data. In addition, leukocyte subsets were classified using single-cell mRNA datasets and flow cytometry (FC). Results IHC revealed characteristic leukocyte distribution patterns based on CD68 and CD163 expression. CD68 hi CD163 lo and CD68 hi CD163 hi cells accumulated close to tumor foci, whereas CD68 lo CD163 hi cells were more evenly distributed in the tumor stroma. PD-L1 hi and PD-1 hi cells accumulated predominantly near tumor foci. High PD-L1 hi CD68 hi CD163 hi or PD-1 hi T cell density near tumor sites correlated with improved survival. FC and RNA analysis showed a high heterogeneity of CD68/CD163 subsets. CD68 hi CD163 lo and CD68 hi CD163 hi cells were primarily macrophages (MΦ), while CD68 lo CD163 hi cells were mainly formed by dendritic cells (DCs). Differentiation by CD64, CD80, CD163 and CD206 indicated a different polarization within macrophages (MΦ). MΦ expressed predominantly CD206 and little CD80. The opposite was observed in DCs. Conclusion Spatial distribution, cell interactions and surface protein expression indicate different roles of CD68/CD163 subsets in the HNSCC microenvironment. Whether PD-L1/PD-1 interactions positively or negatively affect survival depends on the type and localization of interacting cells. These results emphasize the relationship between the spatial distribution of leukocytes and the clinical presentation of HNSCC. Funding information CN was funded by the DFG as part of the Clinician Scientist Programme \"Cell Dynamics in Disease and Therapy\" (project number 413501650) and the Else-Kröner-Forschungskolleg Göttingen \"Molecular Therapy and Prediction in Gastrointestinal Malignancies\" at the University Medical Center Göttingen. AW was supported by the "Deutsche Krebshilfe" (70114051), the "LOEWE-Zentrum Frankfurt Cancer Institute (FCI)" and the EnABLE Cluster (both funded by the "Hessisches ministerium für Wissenschaft und Kunst"). Publication History Article published online: 19 April 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.