ArticleJournal of experimental & clinical cancer research : CR2024
NK cell-triggered CCL5/IFNγ-CXCL9/10 axis underlies the clinical efficacy of neoadjuvant anti-HER2 antibodies in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 29 citations in OpenAlex.
- The peripheral immune landscape of human breast cancer.Oncoimmunology · 2026Review
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Unveiling CCL5: the master regulator of breast cancer progression and immune evasion.Breast cancer research : BCR · 2026Review
- Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.Cancer cell international · 2026Review
- Lactate-Driven IL8+ Tumor-Associated Macrophages Mediate Immunosuppression and Resistance to Immunotherapy in Clear-Cell Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Characteristics of NK cells activation following IL-12, IL-15, IL-18 cytokines stimulation for preclinical purposes.Scientific reports · 2026Article
- Phenotypic alterations in the immune system and tolerance induction in tumor-draining lymph nodes.Iranian journal of basic medical sciences · 2026Review
- CCL5Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pan-cancer NK cell-related immunotherapy signatures for predicting PD-1 treatment response.Medicine · 2025Article
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- CXCL9 is a dual‑role biomarker in colorectal cancer linked to mitophagy and modulated by ALKBH5.Molecular medicine reports · 2025Article
- Epacadostat Overcomes Cetuximab Resistance in Colorectal Cancer by Targeting IDO-Mediated Tryptophan Metabolism.Cancer science · 2025Article
- Secretome and Cellular Composition of Peripheral Blood Mononuclear Cells Cultured in the Presence of Cell Feeder or Interleukins.Bulletin of experimental biology and medicine · 2025Article
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis.Biomedicines · 2025Article
- Frizzled-7-targeting antibody-derived bifunctional protein retargets NK cells against triple-negative breast cancer cells via MICA-NKG2D axis.Journal for immunotherapy of cancer · 2025Article
- Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases.Scientific reports · 2025Article
- An insight into the role of innate immune cells in breast tumor microenvironment.Breast cancer (Tokyo, Japan) · 2025Review
- Current state of cancer immunity cycle: new strategies and challenges of using precision hydrogels to treat breast cancer.Frontiers in immunology · 2025Review
- Single-Nucleus and Bulk RNA Sequencing Reveals the Involvement of Natural Killer and CD8Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundThe variability in responses to neoadjuvant treatment with anti-HER2 antibodies prompts to personalized clinical management and the development of innovative treatment strategies. Tumor-infiltrating Natural Killer (TI-NK) cells can predict the efficacy of HER2-targeted antibodies independently from clinicopathological factors in primary HER2-positive breast cancer patients. Understanding the mechanism/s underlying this association would contribute to optimizing patient stratification and provide the rationale for combinatorial approaches with immunotherapy.
methodsWe sought to uncover processes enriched in NK cell-infiltrated tumors as compared to NK cell-desert tumors by microarray analysis. Findings were validated in clinical trial-derived transcriptomic data. In vitro and in vivo preclinical models were used for mechanistic studies. Findings were analysed in clinical samples (tumor and serum) from breast cancer patients.
resultsNK cell-infiltrated tumors were enriched in CCL5/IFNG-CXCL9/10 transcripts. In multivariate logistic regression analysis, IFNG levels underlie the association between TI-NK cells and pathological complete response to neoadjuvant treatment with trastuzumab. Mechanistically, the production of IFN-ɣ by CD16
conclusionsThis study identifies specialized NK cell subsets as the source of IFN-ɣ influencing the clinical efficacy of anti-HER2 antibodies. It also reveals the potential of serum CCL5/CXCL9 as biomarkers for identifying patients with NK cell-rich tumors and favorable responses to anti-HER2 antibody-based neoadjuvant treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.