ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
CXCR4-modified CAR-T cells suppresses MDSCs recruitment via STAT3/NF-κB/SDF-1α axis to enhance efficacy against pancreatic cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Single-cell RNA sequencing uncovers an immunosuppressive program in PDAC mast cells: tumour-driven activation, proliferation, and association with Treg recruitment.Annals of medicine · 2026Article
- Multifaceted roles of chemokines in gastric cancer: From tumor microenvironment modulation to therapeutic targeting (Review).Oncology letters · 2026Review
- M1 macrophage-derived CXCL12 drives neurogenic heterotopic ossification following spinal cord injury.Neural regeneration research · 2026Article
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.Translational cancer research · 2026Article
- CX3CR1⁺ CD8⁺ cytotoxic T cells drive tumor killing in esophageal squamous cell carcinoma during neoadjuvant therapy.Nature communications · 2026Article
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- S100A14 in Tumor-Derived EVs Targets PIAS3 to Reprogram Astrocytes and Induce Immunosuppressive Microenvironment Promoting Brain Metastasis and Germacrone Reversal Effect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exosome-mediated regulation of the immune microenvironment via JAK/STAT signaling promotes pancreatic cancer progression.Translational cancer research · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Epitranscriptomic silencing of the ZC3H13/mJournal of experimental & clinical cancer research : CR · 2026Article
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Xiaotan Sanjie recipe suppressed the oncogenic potential of cancer-associated fibroblaststhe stromal-derived factor 1α/C-X-C chemokine receptor type 4 pathway in gastric cancer.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.Cancers · 2026Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Claudin18.2 (CLDN18.2)-specific chimeric antigen receptor (CAR-T) cells displayed limited efficacy in CLDN18.2-positive pancreatic ductal adenocarcinoma (PDAC). Strategies are needed to improve the trafficking capacity of CLDN18.2-specific CAR-T cells. PDAC has a unique microenvironment that consists of abundant cancer-associated fibroblasts (CAFs), which could secrete stromal cell-derived factor 1α (SDF-1α), the ligand of CXCR4. Then, we constructed and explored CLDN18.2-targeted CAR-T cells with CXCR4 co-expression in treating immunocompetent mouse models of PDAC. The results indicated that CXCR4 could promote the infiltration of CAR-T cells and enhance their efficacy in vivo. Mechanistically, the activation of signal transducer and activator of transcription 3 (STAT3) signaling was impaired in CXCR4 CAR-T cells, which reduced the release of inflammatory factors, such as tumor necrosis factor-α, IL-6, and IL-17A. Then, the lower release of inflammatory factors suppressed SDF-1α secretion in CAFs via the nuclear factor κB (NF-κB) pathway. Therefore, the decreased secretion of SDF-1α in feedback decreased the migration of myeloid-derived suppressor cells (MDSCs) in tumor sites. Overall, our study demonstrated that CXCR4 CAR-T cells could traffic more into tumor sites and also suppress MDSC migration via the STAT3/NF-κB/SDF-1α axis to obtain better efficacy in treating CLDN18.2-positive pancreatic cancer. Our findings provide a theoretical rationale for CXCR4 CAR-T cell therapy in PDAC.
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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.