ArticleThe journal of pathology. Clinical research2022
Homologous recombination deficiency is inversely correlated with microsatellite instability and identifies immunologically cold tumors in most cancer types.
Article in The journal of pathology. Clinical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- A Phase II Pilot Study of Anti-PD-L1, Durvalumab, and a PARP Inhibitor, Olaparib in Patients With Metastatic Triple-Negative Breast Cancer With or Without Germline BRCA Mutation.Cancer medicine · 2025Trial
- Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2-negative metastatic breast cancer.Cancer immunology, immunotherapy : CII · 2024Trial
- Prognostic implications of tissue-based homologous recombination deficiency in metastatic gastric cancer treated with immune checkpoint inhibitor plus chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Role of clonal lineage analysis via next-generation sequencing in identifying the origin of multiple cancers and guiding treatment options.Japanese journal of clinical oncology · 2026Article
- Whole genome sequencing approach to assess homologous recombination deficiency in a pan-cancer cohort.Communications medicine · 2026Article
- Evaluation of the 1021-HRD assay compared to established HRD testing platforms in ovarian cancer.Translational oncology · 2026Article
- Nationwide comprehensive genomic profiling defines the genomic landscape of hepatocellular carcinoma across etiologies.Scientific reports · 2025Article
- The distinct landscape of tumor immune microenvironment in homologous recombination deficient cancers.Biomarker research · 2025Review
- A Comprehensive Analysis Exploring the Impact of an Immunogenic Cell Death-Related Panel for Ovarian Cancer.Molecular biotechnology · 2025Article
- Retrieval Augmented Therapy Suggestion for Molecular Tumor Boards: Algorithmic Development and Validation Study.Journal of medical Internet research · 2025Article
- Advances in PD-1 and CTLA-4 dual-target immunotherapy for ovarian cancer.Frontiers in immunology · 2025Review
- Pan-Cancer Analysis of Homologous Recombination Deficiency in Cell Lines.Cancer research communications · 2024Article
- Novel protein-based prognostic signature linked to immunotherapeutic efficiency in ovarian cancer.Journal of ovarian research · 2024Article
- Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma.The journal of pathology. Clinical research · 2024Article
- Towards targeting the breast cancer immune microenvironment.Nature reviews. Cancer · 2024Review
- Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Regression-based Deep-Learning predicts molecular biomarkers from pathology slides.Nature communications · 2024Article
- Multi-scale characterisation of homologous recombination deficiency in breast cancer.Genome medicine · 2023Article
- Current Strategy to Treat Immunogenic Gastrointestinal Cancers: Perspectives for a New Era.Cells · 2023Review
- Upregulated FADD is associated with poor prognosis, immune exhaustion, tumor malignancy, and immunotherapy resistance in patients with lung adenocarcinoma.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homologous recombination deficiency (HRD) leads to DNA double-strand breaks and can be exploited by the use of poly (ADP-ribose) polymerase (PARP) inhibitors to induce synthetic lethality. Extending the original therapeutic concept, the role of HRD is currently being investigated in clinical trials testing immune checkpoint blockers alone or in combination with PARP inhibitors, but the relationship between HRD and immune cell context in cancer is incompletely understood. We analyzed the association between immune cell composition, gene expression, and HRD in 9,041 tumors of 32 solid cancer types from The Cancer Genome Atlas (TCGA). The numbers of genomic scars were quantified by the HRD sum score (HRDsum) including loss of heterozygosity, large-scale state transitions, and telomeric allelic imbalance. The T-cell inflamed gene expression profile correlated weakly, but significantly positively, with HRDsum across cancer types (ρ = 0.17). Within individual cancer types, a significantly positive correlation was observed only in breast cancer, ovarian cancer, and four other cancer types, but not in the remaining 26 cancer types. HRDsum and tumor mutational burden (TMB) correlated significantly positively across cancer types (ρ = 0.42) and within 18 cancer types. HRDsum and a proliferation metagene correlated significantly positively across cancer types (ρ = 0.52) and within 20 cancer types. Mismatch repair deficiency and HRD as well as proofreading deficiency showed a high level of exclusivity. High HRD scores were associated with an immunologically activated tumor microenvironment only in a minority of cancer types. Our data favor the combination of genetic markers, complex genomic markers (including HRDsum and TMB), and other molecular markers (including proliferation scores) for a precise and comprehensive read-out of the tumor biology and an individually tailored treatment.
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