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A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer
Open accessPublished version of a preprint
Abstract
Abstract Background Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed a comprehensive portrait of immunologic landscape of TNBC based on 2 large-scale breast cancer genomic data. Methods We compared expression levels of immune-related genes and gene-sets among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. Moreover, we explored the association of immune-related genes or gene-sets expression and survival prognosis in TNBC patients. Results We found that almost all analyzed immune-related gene-sets had significantly higher expression levels in TNBC than non-TNBC. These highly expressed gene-sets in TNBC included 15 immune cell type and function, human leukocyte antigen (HLA), cancer testis (CT), tumor-infiltrating lymphocytes (TILs), immune cell infiltrate, regulatory T (Treg) cells, immune checkpoint, cytokine and cytokine receptor, metastasis-promoting, pro-inflammatory and parainflammation (PI) gene-sets. Moreover, TP53-mutated , TNBC had significantly higher expression levels of the immune checkpoint, Treg, PI, and CT gene-sets, and lower expression levels of the immune cell infiltrate gene-set than TP53 -wildtype TNBC. Furthermore, we found that elevated expression of most of the immune-related genes in TNBC was associated with the ER-status, while some were associated with both ER-and HER2-status. Elevated expression of the immune-related genes in TNBC was also associated with the high tumor mutation burden (TMB) in TNBC. Finally, elevated expression of the immune-related gene-sets was likely to be associated with better survival prognosis in TNBC. Conclusions Our findings suggest that TNBC is a breast cancer subtype with particularly strong immunogenicity, and therefore could be propitious to immunotherapeutic options.
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“Paradoxically, despite strong immunogenicity and a higher prevalence of tumor-infiltrating lymphocytes (TILs) in TNBC3, patients often progress to metastasis with poor clinical outcomes1.”
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Metadata
- Authors
- Liu, Z., Li, M., Jiang, Z., & Wang, X.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Wang, Xiaosheng
- Venue
- Translational Oncology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 11
- Issue
- 2
- Pages
- 311-329
- ISSN
- 1936-5233 (ISSN-L)
- PMC
- PMC5884188
- OpenAlex
- W2766581433
- Cited by
- 275
- References
- 69
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 22 · 2023: 39 · 2022: 45 · 2021: 51 · 2020: 46 · 2019: 24 · 2018: 9
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Translational Oncology (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- China Pharmaceutical University (2632018YX01, 3150120001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- triple-negative breast cancer, tumor immunogenicity, immune pathways, immunotherapy, breast cancer subtypes, survival prediction, genomic data analysis
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