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<p>Patients with high-grade serous ovarian cancer (HGSOC) typically present with widespread metastasis, obscuring a temporal understanding of tumor-immune dynamics. To address this, we perform multi-site global proteomics alongside matched immunohistochemistry (IHC) for CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs) in patient samples. We order the protein expression profiles using an unbiased pseudotime analysis, recapitulating clinical observations of metastatic progression, and providing a framework to explore tumor-immune dynamics from localized to metastatic disease. Metastatic progression correlates with immune cell infiltration, the recruitment of regulatory T cells (Tregs) to counterbalance γδ T cell abundance, and an increased abundance of exhausted CD8⁺ T cells. The accumulation of Tregs at metastatic sites correlates with SNX8 expression, a critical regulator of the STING pathway. In early-stage tumors, keratin-expressing cancer cells recruit Tregs via MHC class II, fostering an inflammatory phenotype with limited IFNγ production and non-clonally expanded T cells. Together, our findings reveal novel mechanisms of immune escape associated with both localized disease and metastatic progression in HGSOC.</p>

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A temporal model of tumor-immune dynamics during the metastatic progression of high-grade serous ovarian cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月16日

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  • Donagh Egan,
  • Kate Glennon,
  • Ann Treacy,
  • Aurelie Fabre,
  • Janet McCormack,
  • Salisha Hill,
  • Ryan Morrison,
  • Vadim Zhernovkov,
  • Daniel Liebler,
  • Walter Kolch,
  • Donal Brennan

摘要

Patients with high-grade serous ovarian cancer (HGSOC) typically present with widespread metastasis, obscuring a temporal understanding of tumor-immune dynamics. To address this, we perform multi-site global proteomics alongside matched immunohistochemistry (IHC) for CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs) in patient samples. We order the protein expression profiles using an unbiased pseudotime analysis, recapitulating clinical observations of metastatic progression, and providing a framework to explore tumor-immune dynamics from localized to metastatic disease. Metastatic progression correlates with immune cell infiltration, the recruitment of regulatory T cells (Tregs) to counterbalance γδ T cell abundance, and an increased abundance of exhausted CD8⁺ T cells. The accumulation of Tregs at metastatic sites correlates with SNX8 expression, a critical regulator of the STING pathway. In early-stage tumors, keratin-expressing cancer cells recruit Tregs via MHC class II, fostering an inflammatory phenotype with limited IFNγ production and non-clonally expanded T cells. Together, our findings reveal novel mechanisms of immune escape associated with both localized disease and metastatic progression in HGSOC.