ArticleCancers2021
RNA-Seq Analysis Reveals CCR5 as a Key Target for CRISPR Gene Editing to Regulate In Vivo NK Cell Trafficking.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
21 citing papers in PubMed, 30 citations in OpenAlex.
- Genome-wide CRISPR screens in primary human natural killer cells identify countermeasures against immunosuppressive environment.Nature communications · 2026Article
- The dual roles of natural killer cells in liver immunity and tolerance: Implications for health and disease.Hepatology communications · 2026Review
- The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026Review
- mRNA processing in cancer immunotherapy: emerging targets, resistance mechanisms, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Robust differentiation of NK cells from MSLN.CAR-IL-15-engineered human iPSCs with enhanced antitumor efficacy against solid tumors.Science advances · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- Redirecting NK cells to the lymph nodes to augment their lymphoma-targeting capacity.NPJ precision oncology · 2024Article
- Article
- Development of NK cell-based cancer immunotherapies through receptor engineering.Cellular & molecular immunology · 2024Review
- The role of CD56Journal of neuroinflammation · 2024Review
- Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy.Frontiers in cell and developmental biology · 2024Review
- Expanded NK cells used for adoptive cell therapy maintain diverse clonality and contain long-lived memory-like NK cell populations.Molecular therapy oncolytics · 2023Article
- Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β.Molecular therapy. Methods & clinical development · 2022Article
- Natural killer cell homing and trafficking in tissues and tumors: from biology to application.Signal transduction and targeted therapy · 2022Review
- Graft-Versus-Solid-Tumor Effect: From Hematopoietic Stem Cell Transplantation to Adoptive Cell Therapies.Stem cells (Dayton, Ohio) · 2022Review
- High-affinity CD16 integration into a CRISPR/Cas9-edited CD38 locus augments CD38-directed antitumor activity of primary human natural killer cells.Journal for immunotherapy of cancer · 2022Article
- Overcoming tumor resistance mechanisms in CAR-NK cell therapy.Frontiers in immunology · 2022Review
- iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A growing number of natural killer (NK) cell-based immunotherapy trials utilize ex vivo expansion to grow and activate allogenic and autologous NK cells prior to administration to patients with malignancies. Recent data in both murine and macaque models have shown that adoptively infused ex vivo expanded NK cells have extensive trafficking into liver tissue, with relatively low levels of homing to other sites where tumors often reside, such as the bone marrow or lymph nodes. Here, we evaluated gene and surface expression of molecules involved in cellular chemotaxis in freshly isolated human NK cells compared with NK cells expanded ex vivo using two different feeder cells lines: Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) or K562 cells with membrane-bound (mb) 4-1BB ligand and interleukin (IL)-21. Expanded NK cells had altered expression in a number of genes that encode chemotactic ligands and chemotactic receptors that impact chemoattraction and chemotaxis. Most notably, we observed drastic downregulation of C-X-C chemokine receptor type 4 (CXCR4) and upregulation of C-C chemokine receptor type 5 (CCR5) transcription and phenotypic expression. clustered regularly interspaced short palindromic repeats (CRISPR) gene editing of CCR5 in expanded NK cells reduced cell trafficking into liver tissue and increased NK cell presence in the circulation following infusion into immunodeficient mice. The findings reported here show that ex vivo expansion alters multiple factors that govern NK cell homing and define a novel approach using CRISPR gene editing that reduces sequestration of NK cells by the liver.
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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.