{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:10:45Z","timestamp":1778217045532,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tumor-associated macrophages (TAMs) belong to the most frequent immune cells in the tumor microenvironment of head and neck squamous cell carcinomas (HNSCC). They can undergo an anti- or pro-tumoral polarization, the latter often referred to as M2-like activation. Because existing data are either not consistent, not well-connected to clinicopathological parameters or lack a detailed spatial distribution, we aimed to get more insight into the relevance of this immune cell population and their activation status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed the spatial distribution and prognostic value of CD68+TAMs and CD68+CD163+M2-like TAMs in different tumor compartments and tumor-distant stromal areas, in 85 treatment-na\u00efve HNSCC. Various clinicopathological features were considered, such as major tumor sites, stage, T-stage, nodal status and p16-status. TAM and M2-like TAM densities were analyzed using multicolor immunofluorescence stainings followed by an objective tissue cytometry-based quantification at the single-cell level in whole tissue sections and subsequent uni- and multivariate survival analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Whereas we observed higher TAM and M2-like TAM densities in p16-negative HNSCC specimens, densities of M2-like TAMs were highest in the tumor-near stroma of advanced nodal-positive p16-negative HNSCC compared to tumor cell nests and tumor-distant stroma, particularly in younger and male patients and patients with hypopharynx carcinomas. Moreover, higher infiltration of M2-like TAMs turned out to be an independent prognostic factor of poorer survival even exceeding the impact of the p16-status and the tumor site.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In summary, our data provide a strong rationale to target M2-like TAMs to improve success of immune-modulatory treatments and survival of patients suffering from p16-negative HNSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1806162","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:34:04Z","timestamp":1778214844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial distribution and prognostic value of tumor-associated macrophages in head and neck squamous cell 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