{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:36:17Z","timestamp":1792787777444,"version":"4.5.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medizinische Hochschule Brandenburg CAMPUS GmbH"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The tumor microenvironment of oropharyngeal squamous cell carcinoma (OPSCC) harbors diverse immune cell populations that influence tumor progression and patient outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>In 102 surgically treated OPSCCs, we determined HPV\/p16 status by immunohistochemistry and RNA in situ hybridization. We analyzed mRNA transcripts using the PanCancer IO360 panel by NanoString.<\/jats:p>\n                    <jats:p>\n                      Multiplex immunohistochemistry\/immunofluorescence was performed to characterize monocytic (M-MDSC, CD11b\u207aCD14\u207aHLA-DR\n                      <jats:sup>low\/\u2212<\/jats:sup>\n                      CD15\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) and polymorphonuclear myeloid derived suppressor cells (PMN-MDSC, CD11b\u207aCD14\n                      <jats:sup>\u2212<\/jats:sup>\n                      HLA-DR\n                      <jats:sup>low\/\u2212<\/jats:sup>\n                      CD15\n                      <jats:sup>+<\/jats:sup>\n                      ), M1-like (CD68\u207aiNOS\u207a) and M2-like macrophages (CD68\u207aCD206\u207a), B cells (CD20\u207a), T helper cells (CD3\u207aCD4\u207a), and cytotoxic T cells (CD3\u207aCD8\u207a) in the tumor (TC) and stroma compartment (SC) of the primary tumor (PT) and the lymph node metastases (LM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic profiling revealed higher lymphoid compartment and antigen presentation scores in HPV\/p16\u207a OPSCC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020, respectively), consistent with increased tumor-infiltrating lymphocytes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025). HPV\/p16\u2013 OPSCC exhibited higher myeloid compartment scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). M2-like macrophages and M-MDSCs were significantly enriched in PT, while M1-like macrophages and PMN-MDSCs predominated in LM (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 each). In HPV\/p16\u2009+\u2009OPSCC, M1-like macrophages, cytotoxic T and B cells were increased (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.050, respectively), whereas MDSC frequencies were comparable between both HPV\/p16 subgroups. Higher PMN-MDSC infiltration was correlated with poorer overall survival (OS,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.050), while increased T helper, cytotoxic T, and B cell infiltration predicted improved OS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HPV\/p16\u2009+\u2009OPSCCs exhibit a lymphoid-dominant, antigen-presenting immune phenotype, whereas HPV\/p16\u2013 tumors display a myeloid-dominated TME. Despite similar MDSC frequencies, transcriptional and spatial analyses suggest functional divergence of myeloid lineages and local immune differentiation between primary and metastatic sites.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-026-01481-w","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:25:51Z","timestamp":1777505151000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Divergent myeloid and lymphoid immune landscapes in HPV\/p16 positive and HPV\/p16 negative oropharyngeal squamous cell carcinomas and their lymph node metastases"],"prefix":"10.1186","volume":"32","author":[{"given":"Raphaela","family":"Graessle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Piwonski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Franzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Olze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja A.","family":"K\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Erben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annekatrin","family":"Coordes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"1481_CR1","unstructured":"Barnes B, Buttmann-Schweiger N, Dahm S, Franke M, Sch\u00f6nfeld I, Kraywinkel K, et al. 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