ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2019
T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 23 citations in OpenAlex.
- Advances in Cancer Immunotherapy for Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immunotherapy resistance in solid tumors: mechanisms and potential solutions.Cancer biology & therapy · 2024Review
- Review
- IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.Cell reports. Medicine · 2024Article
- Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives.Nature reviews. Clinical oncology · 2024Review
- Using unsupervised machine learning to classify behavioral risk markers of bacterial vaginosis.Archives of gynecology and obstetrics · 2024Article
- Triple-Negative Breast Cancer: Tumor Immunogenicity and Beyond.International journal of breast cancer · 2024Review
- Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Tumor immune evasion through loss of MHC class-I antigen presentation.Current opinion in immunology · 2023Review
- Targeting HER2-positive breast cancer: advances and future directions.Nature reviews. Drug discovery · 2023Review
- Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment.Frontiers in immunology · 2023Review
- Functional impact of multi-omic interactions in breast cancer subtypes.Frontiers in genetics · 2022Article
- Emerging immunotherapeutic strategies for the treatment of breast cancer.Breast cancer research and treatment · 2022Review
- Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response.Frontiers in immunology · 2022Review
- Article
- Promises and challenges of adoptive T-cell therapies for solid tumours.British journal of cancer · 2021Review
- The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity.Cell research · 2020Review
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Authors and funding
30 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundTumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancer (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy. PATIENTS AND
methodsWe analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes [metastatic lymph nodes (mLN)] in early BC (EBC) after exposure to T-cell bispecific antibodies (TCB) bridging CD3ε and human epidermal growth factor receptor 2 (HER2) or Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), before and after chemotherapy. Human leukocyte antigen (HLA) class I loss was assessed by whole exome sequencing and immunohistochemistry. One hundred primary BC, 64 surrounding 'healthy tissue' and 24 mLN-related parameters were analyzed.
resultsHLA loss of heterozygosity was observed in EBC, at a clonal and subclonal level and was associated with regulatory T cells and T-cell immunoglobulin and mucin-domain-3 expression restraining the immuno-stimulatory effects of neoadjuvant chemotherapy. TCB bridging CD3ε and HER2 or CEACAM5 could bypass major histocompatibility complex (MHC) class I loss, partially rescuing T-cell functions in mLN.
conclusionTCB should be developed in BC to circumvent low MHC/peptide complexes.
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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.