ArticleCancer immunology research2019
NK Cells Expressing a Chimeric Activating Receptor Eliminate MDSCs and Rescue Impaired CAR-T Cell Activity against Solid Tumors.
Article in Cancer immunology research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 2 of them syntheses that pooled it.
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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
179 citing papers in PubMed, 2 syntheses or guidelines pooled it, 247 citations in OpenAlex.
- Evolution of Immunotherapy for Ovarian Cancer from a Bird's-Eye Perspective: A Text-Mining Analysis of Publication Trends and Topics.Frontiers in oncology · 2022Pooled it
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- Bispecific NK-Cell Engager Targeting TP53 Mutation Through Integration of a TCR-mimic Antibody.MedComm · 2026Article
- Ecosystem-matched reprogramming of the tumor-immune microenvironment to overcome cancer immunotherapy resistance.Molecular cancer · 2026Review
- Epigenetic modulation of NKG2D ligands enhances NKG2D-CAR T cell efficacy in neuroblastoma.Journal of translational medicine · 2026Article
- A bibliometric and visualized analysis of CAR-T or TCR-T in solid tumor (from 2015 to 2024).Discover oncology · 2026Article
- Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.Cancer cell international · 2026Review
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- 2025 Update of Cellular Immunotherapy for Plasma Cell Disorders.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026Review
- Targeted drug delivery strategies for oral cancer: the role of liposomes in drug delivery systems.Biomedical engineering online · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.Frontiers in immunology · 2026Review
- Parallel processing of T cells and natural killer cells to enhanceClinical & translational immunology · 2026Article
- CAR-NK Engineering to Overcome TME Barriers.Cells · 2025Review
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- CAR NK cell therapy for solid tumors: potential and challenges.Antibody therapeutics · 2025Review
- Intraperitoneal infusion of NKG2D CAR-NK cells induces endogenous CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
119 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Solid tumors are refractory to cellular immunotherapies in part because they contain suppressive immune effectors such as myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic lymphocytes. Strategies to reverse the suppressive tumor microenvironment (TME) should also attract and activate immune effectors with antitumor activity. To address this need, we developed gene-modified natural killer (NK) cells bearing a chimeric receptor in which the activating receptor NKG2D is fused to the cytotoxic ζ-chain of the T-cell receptor (NKG2D.ζ). NKG2D.ζ-NK cells target MDSCs, which overexpress NKG2D ligands within the TME. We examined the ability of NKG2D.ζ-NK cells to eliminate MDSCs in a xenograft TME model and improve the antitumor function of tumor-directed chimeric antigen receptor (CAR)-modified T cells. We show that NKG2D.ζ-NK cells are cytotoxic against MDSCs, but spare NKG2D ligand-expressing normal tissues. NKG2D.ζ-NK cells, but not unmodified NK cells, secrete proinflammatory cytokines and chemokines in response to MDSCs at the tumor site and improve infiltration and antitumor activity of subsequently infused CAR-T cells, even in tumors for which an immunosuppressive TME is an impediment to treatment. Unlike endogenous NKG2D, NKG2D.ζ is not susceptible to TME-mediated downmodulation and thus maintains its function even within suppressive microenvironments. As clinical confirmation, NKG2D.ζ-NK cells generated from patients with neuroblastoma killed autologous intratumoral MDSCs capable of suppressing CAR-T function. A combination therapy for solid tumors that includes both NKG2D.ζ-NK cells and CAR-T cells may improve responses over therapies based on CAR-T cells alone.
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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.