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Background <p>The tumor microenvironment of oropharyngeal squamous cell carcinoma (OPSCC) harbors diverse immune cell populations that influence tumor progression and patient outcome.</p> Materials <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.</p> <p>Multiplex immunohistochemistry/immunofluorescence was performed to characterize monocytic (M-MDSC, CD11b⁺CD14⁺HLA-DR<sup>low/−</sup>CD15<sup>−</sup>) and polymorphonuclear myeloid derived suppressor cells (PMN-MDSC, CD11b⁺CD14<sup>−</sup>HLA-DR<sup>low/−</sup>CD15<sup>+</sup>), M1-like (CD68⁺iNOS⁺) and M2-like macrophages (CD68⁺CD206⁺), B cells (CD20⁺), T helper cells (CD3⁺CD4⁺), and cytotoxic T cells (CD3⁺CD8⁺) in the tumor (TC) and stroma compartment (SC) of the primary tumor (PT) and the lymph node metastases (LM).</p> Results <p>Transcriptomic profiling revealed higher lymphoid compartment and antigen presentation scores in HPV/p16⁺ OPSCC (<i>p</i> = 0.002, <i>p</i> = 0.020, respectively), consistent with increased tumor-infiltrating lymphocytes (<i>p</i> = 0.025). HPV/p16– OPSCC exhibited higher myeloid compartment scores (<i>p</i> &lt; 0.001). M2-like macrophages and M-MDSCs were significantly enriched in PT, while M1-like macrophages and PMN-MDSCs predominated in LM (<i>p</i> &lt; 0.001 each). In HPV/p16 + OPSCC, M1-like macrophages, cytotoxic T and B cells were increased (<i>p</i> &lt; 0.001, <i>p</i> &lt; 0.001, <i>p</i> = 0.050, respectively), whereas MDSC frequencies were comparable between both HPV/p16 subgroups. Higher PMN-MDSC infiltration was correlated with poorer overall survival (OS, <i>p</i> = 0.050), while increased T helper, cytotoxic T, and B cell infiltration predicted improved OS (<i>p</i> = 0.009, <i>p</i> &lt; 0.001, <i>p</i> = 0.005, respectively).</p> Conclusion <p>HPV/p16 + OPSCCs exhibit a lymphoid-dominant, antigen-presenting immune phenotype, whereas HPV/p16– 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.</p>

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Divergent myeloid and lymphoid immune landscapes in HPV/p16 positive and HPV/p16 negative oropharyngeal squamous cell carcinomas and their lymph node metastases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Raphaela Graessle,
  • Iris Piwonski,
  • Achim Franzen,
  • Heidi Olze,
  • Anja A. Kühl,
  • Michael Hummel,
  • Ulrike Erben,
  • Annekatrin Coordes

摘要

Background

The tumor microenvironment of oropharyngeal squamous cell carcinoma (OPSCC) harbors diverse immune cell populations that influence tumor progression and patient outcome.

Materials

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.

Multiplex immunohistochemistry/immunofluorescence was performed to characterize monocytic (M-MDSC, CD11b⁺CD14⁺HLA-DRlow/−CD15−) and polymorphonuclear myeloid derived suppressor cells (PMN-MDSC, CD11b⁺CD14−HLA-DRlow/−CD15+), M1-like (CD68⁺iNOS⁺) and M2-like macrophages (CD68⁺CD206⁺), B cells (CD20⁺), T helper cells (CD3⁺CD4⁺), and cytotoxic T cells (CD3⁺CD8⁺) in the tumor (TC) and stroma compartment (SC) of the primary tumor (PT) and the lymph node metastases (LM).

Results

Transcriptomic profiling revealed higher lymphoid compartment and antigen presentation scores in HPV/p16⁺ OPSCC (p = 0.002, p = 0.020, respectively), consistent with increased tumor-infiltrating lymphocytes (p = 0.025). HPV/p16– OPSCC exhibited higher myeloid compartment scores (p < 0.001). M2-like macrophages and M-MDSCs were significantly enriched in PT, while M1-like macrophages and PMN-MDSCs predominated in LM (p < 0.001 each). In HPV/p16 + OPSCC, M1-like macrophages, cytotoxic T and B cells were increased (p < 0.001, p < 0.001, p = 0.050, respectively), whereas MDSC frequencies were comparable between both HPV/p16 subgroups. Higher PMN-MDSC infiltration was correlated with poorer overall survival (OS, p = 0.050), while increased T helper, cytotoxic T, and B cell infiltration predicted improved OS (p = 0.009, p < 0.001, p = 0.005, respectively).

Conclusion

HPV/p16 + OPSCCs exhibit a lymphoid-dominant, antigen-presenting immune phenotype, whereas HPV/p16– 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.