ArticleAnnals of surgical oncology2019
Tumor Heterogeneity Correlates with Less Immune Response and Worse Survival in Breast Cancer Patients.
Article in Annals of surgical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
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Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Neoantigens elicit T cell responses in breast cancer.Scientific reports · 2021Trial
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Review
- Exploratory biomarker findings from regorafenib plus toripalimab in patients with refractory metastatic colorectal cancer (REGOTORI study).Gastroenterology report · 2026Article
- NeoPrecis: enhancing immunotherapy response prediction through integration of qualified immunogenicity and clonality-aware neoantigen landscapes.Nature communications · 2026Article
- Dual cutoffs of estrogen receptor positivity define prognostic and predictive subgroups in breast cancer.iScience · 2026Article
- Oncolytic viruses in lung cancer: mechanisms of action and research progress.Frontiers in microbiology · 2026Review
- Genomic diversity and BCL9L mutational status in circulating tumor cells predict overall survival in metastatic colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- DEPTH2 score was associated with cell proliferation and immune cell infiltrations but not with systemic treatment response in breast cancer.Scientific reports · 2025Article
- Integrated spatial proteomic analysis of breast cancer heterogeneity unravels cancer cell phenotypic plasticity.Nature communications · 2025Article
- Invasive Lobular Carcinoma Has Higher Immune Response Than Invasive Ductal Carcinoma in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers.World journal of oncology · 2025Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- NeoPrecis: Enhancing Immunotherapy Response Prediction through Integration of Qualified Immunogenicity and Clonality-Aware Neoantigen Landscapes.bioRxiv : the preprint server for biology · 2025Article
- High intratumoral heterogeneity in clear cell renal cell carcinoma is associated with reduced immune response and survival.Translational andrology and urology · 2025Article
- Cancer immune evasion, immunoediting and intratumour heterogeneity.Nature reviews. Immunology · 2025Review
- The American Joint Committee on Cancer (AJCC) Breast Cancer Staging, Eighth Edition, is more Reflective of Cancer Biology than the Seventh Edition.Annals of surgical oncology · 2025Article
- Review
- Article
- From Images to Genes: Radiogenomics Based on Artificial Intelligence to Achieve Non-Invasive Precision Medicine in Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIntratumor heterogeneity implies that subpopulations of cancer cells that differ in genetic, phenotypic, or behavioral characteristics coexist in a single tumor (Ma in Breast Cancer Res Treat 162(1):39-48, 2017; Martelotto in Breast Cancer Res 16(3):210, 2014). Tumor heterogeneity drives progression, metastasis and treatment resistance, but its relationship with tumor infiltrating immune cells is a matter of debate, where some argue that tumors with high heterogeneity may generate neoantigens that attract immune cells, and others claim that immune cells provide selection pressure that shapes tumor heterogeneity (McGranahan et al. in Science 351(6280):1463-1469, 2016; McGranahan and Swanton in Cell 168(4):613-628, 2017). We sought to study the association between tumor heterogeneity and immune cells in a real-world cohort utilizing The Cancer Genome Atlas.
methodsMutant allele tumor heterogeneity (MATH) was calculated to estimate intratumoral heterogeneity, and immune cell compositions were estimated using CIBERSORT. Survival analyses were demonstrated using Kaplan-Meir curves.
resultsTumors with high heterogeneity (high MATH) were associated with worse overall survival (p = 0.049), as well as estrogen receptor-positive (p = 0.011) and non-triple-negative tumors (p = 0.01). High MATH tumors were also associated with less infiltration of anti-tumor CD8 (p < 0.013) and CD4 T cells (p < 0.00024), more tumor-promoting regulatory T cells (p < 4e-04), lower expression of T-cell exhaustion markers, specifically PDL-1 (p = 0.0031), IDO2 (p = 0.34), ADORA2A (p = 0.018), VISTA (p = 0.00013), and CCR4 (p < 0.00001), lower expression of cytolytic enzymes granzyme A (p = 0.0056) and perforin 1 (p = 0.053), and low cytolytic activity score (p = 0.0028).
conclusionsHigh heterogeneity tumors are associated with less immune cell infiltration, less activation of the immune response, and worse survival in breast cancer. Our results support the notion that tumor heterogeneity is shaped by selection pressure of tumor-infiltrating immune cells.
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