Evidence map›Paper›PMID 41279139›Full record

ArticlebioRxiv : the preprint server for biology2025

Tissue specificity and chromosomal alterations shape divergent immune programs in HRD tumors.

Doga C Gulhan, David Barras, Marco Mina, Eleonora Ghisoni, Yoo-Na Kim, Vinay Viswanadham, Hu Jin, Florian Huber, Krisztian Homicsko, Michal Bassani-Sternberg and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Doga C GulhanKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.ORCID 0000-0001-5419-0549
David BarrasDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0001-8985-4704
Marco MinaDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-4186-8995
Eleonora GhisoniDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0009-0007-1135-2377
Yoo-Na KimKrantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, USA.ORCID 0000-0002-0202-3228
Vinay ViswanadhamDepartment of Biomedical Informatics, Harvard Medical School, Boston, USA.ORCID 0000-0002-0236-6490
Hu JinDepartment of Biomedical Informatics, Harvard Medical School, Boston, USA.ORCID 0000-0002-8657-5686
Florian HuberDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-2585-9079
Krisztian HomicskoDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0003-0912-6198
Michal Bassani-SternbergDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-1934-954X
Giovanni CirielloDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0003-2021-8683
Peter J ParkDepartment of Biomedical Informatics, Harvard Medical School, Boston, USA.ORCID 0000-0001-9378-960X
Denarda Dangaj LanitiDepartment of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-5659-6427

Funding

Mutational signature analysis: methods and applications to the clinicR01CA269805 · NCI · HARVARD MEDICAL SCHOOL · PI Peter J Park · 2022 to 2026
$2.2M
NCI NIH HHS R01 CA269805
6 · The paper itself

Abstract

Homologous recombination deficiency (HRD) activates pro-inflammatory cGAS/STING signaling, positioning it as a biomarker for combining immune checkpoint blockade (ICB) and PARP inhibition (PARPi). However, the consequences of HRD on the immune landscape across cancers remain unclear. Here, we applied a pan-cancer HRD classifier to >10,000 tumors from The Cancer Genome Atlas and uncovered striking heterogeneity in immune activity. Compared to HR-proficient tumors, HRD tumors showed elevated inflammation in breast, ovarian, and endometrial cancers. These tumors exhibited robust activation of innate and adaptive immune pathways (IFN, NF-κB) and transcriptional hallmarks of senescence, angiogenesis, and adenosine signaling. In contrast, lung, head and neck, and melanoma HRD tumors displayed suppressed inflammation and evidence of immune escape through large-scale loss-of-heterozygosity (LOH) at IFNA/B, STING, and other loci. These tumors also frequently presented HLA LOH and oncogene amplifications, suggesting selection under immune pressure and replication stress. Together, our study resolves HRD tumors into two immune archetypes, immune-inflamed and immune-evasive, linked to chromosomal instability and lineage, informing biomarker-driven evaluation of immune checkpoint blockade/PARPi combinatorial therapies.

Identifiers

PMID41279139
PMCPMC12633024

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