ArticleOncogenesis2021
Suppression of 4.1R enhances the potency of NKG2D-CAR T cells against pancreatic carcinoma via activating ERK signaling pathway.
Article in Oncogenesis, 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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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- TIPE2 knockdown enhances the anti-tumor efficacy of NKG2D CAR-T cells against pancreatic cancer via activating NF-κb signaling pathway.Journal of translational medicine · 2026Article
- NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.Frontiers in immunology · 2026Review
- Advanced strategies to enhance the safety, persistence, and efficacy of CAR-T cells in solid tumors.Frontiers in immunology · 2026Review
- GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint.Science advances · 2025Article
- Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies.Cancers · 2025Review
- Looking Beyond Checkpoint Inhibitor Monotherapy: Uncovering New Frontiers for Pancreatic Cancer Immunotherapy.Molecular cancer therapeutics · 2025Review
- TCR-T cell therapy for solid tumors: challenges and emerging solutions.Frontiers in pharmacology · 2025Review
- Harnessing NKG2D CAR-T cells with radiotherapy: a novel approach for esophageal squamous cell carcinoma treatment.Frontiers in immunology · 2025Article
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- Co-expression of IL-15/IL-15Ra complex enhances NKG2D-CAR T cell-mediated anti-pancreatic cancer immunity by activating the JAK/STAT5 signaling pathway.Frontiers in immunology · 2025Article
- Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Article
- Chimeric Antigen Receptor T Cell Therapy for Pancreatic Cancer: A Review of Current Evidence.Cells · 2024Review
- A novel strategy of co-expressing CXCR5 and IL-7 enhances CAR-T cell effectiveness in osteosarcoma.Frontiers in immunology · 2024Article
- shRNA-mediated gene silencing of HDAC11 empowers CAR-T cells against prostate cancer.Frontiers in immunology · 2024Article
- β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy.International journal of molecular sciences · 2023Review
- Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8Cancer immunology, immunotherapy : CII · 2023Article
- Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors. 4.1R has been reported to suppress the anti-tumor activity of T cell responses. In this study, we investigated the anti-tumor activity of 4.1R deletion in natural killer group 2D (NKG2D)-CAR T cells against PC. The CAR T cells were obtained by transfecting T cells with lentiviral vector carrying NKG2D-CAR, NC-NKG2D-CAR, or KD2-NKG2D-CAR. In vitro, NKG2D-CAR T cells showed higher cytotoxicity than Mock T cells. However, compared to NKG2D-CAR T cells, furtherly higher cytotoxicity against PC cells in a dose-dependent manner was found in KD2-NKG2D-CAR T cells. In addition, the proliferation rate and cytotoxic activity of KD2-NKG2D-CAR T cells were significantly higher than those of NKG2D-CAR T cells. Besides, the inhibitory receptors PD-1 and TIM-3 were expressed in lower level on KD2-NKG2D-CAR T cells. In vivo, KD2-NKG2D-CAR T cells suppressed tumor growth more effectively in a xenograft model compared to NKG2D-CAR T cells. Mechanistically, 4.1R regulated CAR T cell function via activating ERK signaling pathway. Therefore, the study provides a new idea to enhance the anti-tumor efficiency of CAR T therapy.
Identifiers
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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.