ArticleCancers2021
ADCC-Inducing Antibody Trastuzumab and Selection of KIR-HLA Ligand Mismatched Donors Enhance the NK Cell Anti-Breast Cancer Response.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- KIR-HLA Functional Repertoire Influences Trastuzumab Efficiency in Patients With HER2-Positive Breast Cancer.Frontiers in immunology · 2021Trial
- Review
- Characterization of ex vivo expanded natural killer cells for cancer immunotherapy.Immunology and cell biology · 2025Article
- Natural killer cells occupy unique spatial neighborhoods in HER2Breast cancer research : BCR · 2025Article
- Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC.Journal of pharmaceutical analysis · 2024Article
- Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.Current molecular medicine · 2024Article
- Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous carcinoma cell lines.Journal of cancer research and clinical oncology · 2023Article
- NK cells direct the perspective approaches to cancer immunotherapy.Medical oncology (Northwood, London, England) · 2023Review
- Exploring the potential of combining IL-2-activated NK cells with an anti-PDL1 monoclonal antibody to target multiple myeloma-associated macrophages.Cancer immunology, immunotherapy : CII · 2023Article
- Inhibitory receptors for HLA class I as immune checkpoints for natural killer cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2023Review
- Antibody-dependent cellular cytotoxicity-inducing antibodies enhance the natural killer cell anti-cancer response against patient-derived pancreatic cancer organoids.Frontiers in immunology · 2023Article
- What Inhibits Natural Killers' Performance in Tumour.International journal of molecular sciences · 2022Review
- Therapeutic strategies for gastric cancer targeting immune cells: Future directions.Frontiers in immunology · 2022Review
- Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer.Frontiers in immunology · 2022Review
- Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK)-cell-based immunotherapies are an attractive treatment option for cancer. We previously showed that alloreactive mouse NK cells cured mice of 4T1 breast cancer. However, the tumor microenvironment can inhibit immune responses, and these suppressive factors must be overcome to unfold the NK cells' full anti-tumor potential. Here, we investigated the combination of antibody-dependent cellular cytotoxicity (ADDC) and the selection of KIR-HLA-ligand mismatched NK cells to enhance NK cell anti-breast cancer responses in clinically relevant settings. Donor-derived and IL-2-activated NK cells were co-cultured with patient-derived breast cancer cells or cell lines MCF7 or SKBR3 together with the anti-HER2 antibody trastuzumab. NK cells mediated anti-breast cancer cytotoxicity under normoxic and hypoxic conditions. Under both conditions, trastuzumab vigorously enhanced NK cell degranulation (CD107a) against HER2-overexpressing SKBR3 cells, but we observed a discrepancy between highly degranulating NK cells and a rather modest increase in cytotoxicity of SKBR3. Against patient-derived breast cancer cells, the anti-tumor efficacy was rather limited, and HLA class I expression seemed to contribute to inhibited NK cell functionality. KIR-ligand-mismatched NK cells degranulated stronger compared to the matched NK cells, further highlighting the role of HLA. In summary, trastuzumab and KIR-ligand-mismatched NK cells could be two strategies to potently enhance NK cell responses to breast cancer.
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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.