Single-cell spatial atlas of high-grade serous ovarian cancer uncovers MHC class II as a key predictor of spatial tumor ecosystems and clinical outcomes
The tumor microenvironment in high-grade serous ovarian carcinoma (HGSC) is a complex network of malignant-host cell interactions, yet its orchestration remains poorly understood. We present a single-cell spatial atlas of metastatic HGSC from 280 patients, integrating high-dimensional imaging and molecular profiling. Analyzing 929 single-cell maps, we identify spatial domains with diverse cell compositions and show that immune cell co-infiltration at the tumor-stroma interface impacts clinical outcomes. Using CEFIIRA, we find that tumor cell MHCII expression is a key predictor of prolonged survival. Validation with deconvoluted, single-cell, and two distinct spatial transcriptomic datasets, along with immunopeptidomic analysis, confirms that MHCII expression correlates with immune activation, antigen presentation, and TCR clonality. Using a patient-derived immuno-oncology platform, we demonstrate that tumor MHCII expression associates with increased CD8+ T cell cytotoxicity after PD-1 blockade, while blocking MHCII inhibits this activation. Our atlas offers new insights into immune activation, potentially improving patient stratification in HGSC.
Authors
- Iga Niemiec (ORCID: https://orcid.org/0000-0002-6134-5083)
- María Mercedes Hincapié-Otero (ORCID: https://orcid.org/0000-0001-8750-1729)
- Matías Marín Falco (ORCID: https://orcid.org/0000-0002-6813-0050)
- Julia Casado (ORCID: https://orcid.org/0000-0002-3662-8794)
- P. Sorger
- Ican Ican
- Vincenzo Cerullo (ORCID: https://orcid.org/0000-0003-4901-3796)
- Lilian van Wagensveld (ORCID: https://orcid.org/0000-0003-4036-3554)
- Salvatore Russo (ORCID: https://orcid.org/0000-0002-0287-0048)
- Joseph Ndika (ORCID: https://orcid.org/0000-0003-0669-1300)
- Gayani Anandagoda (ORCID: https://orcid.org/0000-0003-4122-3561)
- Matilda Salko (ORCID: https://orcid.org/0000-0003-2548-8017)
- Mikaela Grönholm (ORCID: https://orcid.org/0000-0002-2378-8924)
- Duco Gaillard (ORCID: https://orcid.org/0009-0009-1946-4247)
- Ella Anttila (ORCID: https://orcid.org/0000-0001-8526-4934)
- Ziqi Kang
- Jacopo Chiaro (ORCID: https://orcid.org/0000-0001-6577-2691)
- Anni Virtanen (ORCID: https://orcid.org/0000-0002-7467-8434)
- Anna Vähärautio (ORCID: https://orcid.org/0000-0003-4721-3954)
- Anniina Färkkilä (ORCID: https://orcid.org/0000-0002-3558-6617)
- Aleksandra Shabanova (ORCID: https://orcid.org/0000-0003-0664-6550)
- Otto K. Kari (ORCID: https://orcid.org/0000-0002-1201-5010)
- Eric Marcus (ORCID: https://orcid.org/0000-0002-3375-6248)
- Ada Junquera
- Gabe S. Sonke
- Foteini Chamchougia
- Saundarya Shah
- Fernando Perez-Villatoro
- Sarah Wolf
- Maaike van der Aa
- Essi Kahelin
- Koen K Van de Vijver
- Kürşat Birgin
- Rutgerus Fpm Kruitwagen
Institutions
- University of Helsinki (FI)
- Harvard University (US)
- Dutch Cancer Society (NL)
- Helsinki University Hospital (FI)
- Ghent University Hospital (BE)
- Harvard University Press (US)
- University of Massachusetts Boston (US)
- Maastricht University (NL)
- Oncode Institute (NL)
- Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NL)
- Dana-Farber/Harvard Cancer Center (US)
- Netherlands Comprehensive Cancer Organisation (NL)
- Io Therapeutics (United States) (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2026-02-09
- DOI
- https://doi.org/10.1158/2159-8290.cd-25-1492
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00