ArticleBlood2024
T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 22 citations in OpenAlex.
- Epigenetic activation of NK-cell effector programs and caspase-8-dependent apoptosis mediates the antitumor activity of LGP in NSCLC.Journal of ginseng research · 2026Article
- TBL1XR1 mutations promoted tumor progression in diffuse large B-cell lymphoma through impairing nature killer cytotoxicity via the MYC-CD47/PD-L1 axis.Molecular cancer · 2026Article
- Efficacy of high-frequency low-dose rituximab and acalabrutinib in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Integration Analysis of Bayesian and Machine Learning for Heterogeneity, Biomarkers, and Optimal Combination Regimens of Pucotenlimab in Solid Tumors.Cancer medicine · 2026Article
- Engineering tandem VHHs to target different epitopes to enhance antibody-dependent cell-mediated cytotoxicity.FEBS open bio · 2026Article
- The novel CD16A/anti-CD3 bifunctional protein, eCD16A/anti-CD3-BFP, redirects T cell cytotoxicity toward antibody-bound target cells.Human vaccines & immunotherapeutics · 2025Article
- Restoring NK Cell Cytotoxicity Post-Cryopreservation via Synthetic Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intestinal reengineering: Scientific advances in intestinal transplantation.World journal of gastrointestinal surgery · 2025Review
- Chimeric antigen receptor natural killer (CAR-NK) cells: from preclinical promise to clinical reality in cancer immunotherapy.Immunotherapy · 2025Review
- Prospects and applications of NK therapy in the treatment of gliomas (Review).Oncology reports · 2025Review
- CAR Beyond αβ T Cells: Unleashing NK Cells, Macrophages, and γδ T Lymphocytes Against Solid Tumors.Vaccines · 2025Review
- The DCDC2/ENO1 axis promotes tumor progression and immune evasion in intrahepatic cholangiocarcinoma via activating FGL1-LAG3 checkpoint.Journal of experimental & clinical cancer research : CR · 2025Article
- Co-expression of IL-15 and CCL21 strengthens CAR-NK cells to eliminate tumors in concert with T cells and equips them with PI3K/AKT/mTOR signal signature.Journal for immunotherapy of cancer · 2025Article
- Integrative machine learning identifies robust inflammation-related diagnostic biomarkers and stratifies immune-heterogeneous subtypes in Kawasaki disease.Pediatric rheumatology online journal · 2025Article
- T-cell activation enhances anti-HER2-mediated antibody-dependent cellular cytotoxicity in gastric cancer.Immunologic research · 2025Article
- Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression.Biomarker research · 2025Review
- CD40L and IL-4 suppress NK cell-mediated antibody-dependent cellular cytotoxicity through the HLA-E:NKG2A axis.Immunotherapy advances · 2025Article
- Targeting CD16A on NK cells and GPC3 in hepatocellular carcinoma: development and functional validation of a therapeutic bispecific antibody.Frontiers in immunology · 2025Article
- ADCC: the rock band led by therapeutic antibodies, tumor and immune cells.Frontiers in immunology · 2025Review
- Master regulator: p53's pivotal role in steering NK-cell tumor patrol.Frontiers in immunology · 2024Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
abstractRituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T-cell help contribute to RTX-mediated NK-cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T-cell numbers in the lymphoma TME. In this model, NK-cell viability and CD16 and CD25 expression dropped after RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In patients with indolent lymphoma, fine needle aspirates were obtained before and ∼1 week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.
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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.