ArticleJournal for immunotherapy of cancer2019
Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
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- The metastatic role of the CXCL10-CXCR3 axis and its therapeutic potential in osteosarcoma.Journal of bone oncology · 2025Article
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- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Inhibition of TIGIT on NK cells improves their cytotoxicity and HIV reservoir eradication potential.mBio · 2025Article
- Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis.Circulation research · 2025Article
- CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors.Cellular & molecular immunology · 2024Review
- Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.Pharmaceutics · 2024Review
- [Research progress of tumor-infiltrating lymphocytes in malignant hematological diseases].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Review
- Image-based assessment of natural killer cell activity against glioblastoma stem cells.FEBS open bio · 2024Article
- Natural killer cell-related anti-tumour adoptive cell immunotherapy.Journal of cellular and molecular medicine · 2024Review
- Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM).Cell communication and signaling : CCS · 2024Review
- Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Article
- Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.Frontiers in cell and developmental biology · 2024Review
- Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy.Frontiers in cell and developmental biology · 2024Review
- CXCR4 has a dual role in improving the efficacy of BCMA-redirected CAR-NK cells in multiple myeloma.Frontiers in immunology · 2024Article
- Chimeric antigen receptor engineered natural killer cells for cancer therapy.Experimental hematology & oncology · 2023Review
- Suppression of CD56Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe peculiar multiple myeloma microenvironment, characterized by up-regulated levels of several inflammatory chemokines, including the CXCR3 receptor ligands CXCL9 and CXCL10, limits NK cell positioning into the bone marrow by interfering with CXCR4 function. It is still unclear if the consequent reduced influx of transferred cells into the tumor represents a potential limiting factor for the success of NK cell-based adoptive therapy. We hypothesize that inhibition of CXCR3 function on NK cells will result in increased tumor clearance, due to higher NK cell bone marrow infiltration.
methodsSince different activation protocols differently affect expression and function of homing receptors, we analyzed the bone marrow homing properties and anti-tumor efficacy of NK cells stimulated in vitro with two independent protocols. NK cells were purified from wild-type or Cxcr3
resultsBoth activation protocols promoted degranulation and IFN-γ production by donor NK cells infiltrating the bone marrow of tumor-bearing mice, although IL-15 promoted a faster but more transient acquisition of functional capacities. In addition, IL-15-activated cells accumulated more in the bone marrow in a short time but showed lower persistence in vivo. Targeting of CXCR3 increased the bone marrow homing capacity of IL-15 but not IL12/15/18 activated NK cells. This effect correlated with a superior and durable myeloma clearance capacity of transferred cells in vivo.
conclusionsOur results demonstrate that in vitro activation affects NK cell anti-myeloma activity in vivo by regulating their BM infiltration. Furthermore, we provided direct evidence that CXCR3 restrains NK cell anti-tumor capacity in vivo according to the activation protocol used, and that the effects of NK cell-based adoptive immunotherapy for multiple myeloma can be improved by increasing their bone marrow homing through CXCR3 inhibition.
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