Myelonets define spatiotemporal immunosuppressive programs in ovarian cancer

Abstract

High-grade serous ovarian carcinoma (HGSC) responds poorly to immune checkpoint blockade, partly due to a macrophage-dominated immunosuppressive microenvironment. We integrated single-cell spatial proteomics and spatial transcriptomics across 50 HGSC tumors and applied SPACEstat to resolve higher-order immune communities and their transcriptional programs. We identified six immune community types, with macrophage-dominated Myelonets representing the predominant spatial pattern of immune organisation. In chemotherapy-exposed tumors, Myelonets showed coordinated lipid metabolism-immunosuppression and inflammation-MHC-II macrophage transcriptional programs, with SPP1, C1Q, VEGF, MMPs, and CCL18 linked to immunosuppressive states and fibroblasts emerging as key mediators of macrophage communication. Chemotherapy contracted large Myelonets while increasing CD8+ T-cell organization into Lymphonets. Persistent macrophage dominance within Myelonets was associated with adverse outcomes among patients who achieved a complete response to treatment. Together, we identify Myelonets as clinically relevant, multicellular immunoregulatory niches sustained by spatiotemporally coordinated macrophage programs and stromal crosstalk.

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Cite

BibTeX RIS

BibTeX

@misc{niemiec2026myelonets,
  title = {{Myelonets define spatiotemporal immunosuppressive programs in ovarian cancer}},
  author = {I. Niemiec and A. Shabanova and E. Ruuska and M. Tissarinen and Z. Liang and G. Anandagoda and S. Shah and Z. Kang and A. Junquera and M. Salko and U.-M. Haltia and A. Virtanen and A. Farkkila},
  howpublished = {medRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.26.26361128},
  url = {https://www.medrxiv.org/content/10.64898/2026.08.26.26361128v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Myelonets define spatiotemporal immunosuppressive programs in ovarian cancer
AU  - I. Niemiec
AU  - A. Shabanova
AU  - E. Ruuska
AU  - M. Tissarinen
AU  - Z. Liang
AU  - G. Anandagoda
AU  - S. Shah
AU  - Z. Kang
AU  - A. Junquera
AU  - M. Salko
AU  - U.-M. Haltia
AU  - A. Virtanen
AU  - A. Farkkila
PY  - 2026
DA  - 2026/08/26
PB  - medRxiv
DO  - 10.64898/2026.08.26.26361128
UR  - https://www.medrxiv.org/content/10.64898/2026.08.26.26361128v1
AB  - High-grade serous ovarian carcinoma (HGSC) responds poorly to immune checkpoint blockade, partly due to a macrophage-dominated immunosuppressive microenvironment. We integrated single-cell spatial proteomics and spatial transcriptomics across 50 HGSC tumors and applied SPACEstat to resolve higher-order immune communities and their transcriptional programs. We identified six immune community types, with macrophage-dominated Myelonets representing the predominant spatial pattern of immune organisation. In chemotherapy-exposed tumors, Myelonets showed coordinated lipid metabolism-immunosuppression and inflammation-MHC-II macrophage transcriptional programs, with SPP1, C1Q, VEGF, MMPs, and CCL18 linked to immunosuppressive states and fibroblasts emerging as key mediators of macrophage communication. Chemotherapy contracted large Myelonets while increasing CD8+ T-cell organization into Lymphonets. Persistent macrophage dominance within Myelonets was associated with adverse outcomes among patients who achieved a complete response to treatment. Together, we identify Myelonets as clinically relevant, multicellular immunoregulatory niches sustained by spatiotemporally coordinated macrophage programs and stromal crosstalk.
ER  -

Abstract

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