ArticleMolecular cancer2014
CD8+T cell-specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+T cell accumulation in tumors.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Remodeling memory T cells with chemotherapy and immune checkpoint inhibitors as host pre-conditioning to empower in vivo CAR-T therapy.Synthetic and systems biotechnology · 2026Review
- Co-formulation of IL-12 mRNA and doxorubicin in polymeric nanoparticles for simultaneous delivery in murine melanoma.RSC pharmaceutics · 2026Article
- Integrated single-cell and transcriptomic analysis of CD8Translational cancer research · 2026Article
- Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin's lymphoma.Journal for immunotherapy of cancer · 2025Article
- Pan-cancer analysis of T-cell proliferation regulatory genes as potential immunotherapeutic targets.Aging · 2024Article
- Mechanisms governing bystander activation of T cells.Frontiers in immunology · 2024Review
- Virtual Memory CD8Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Bystander T cells in cancer immunology and therapy.Nature cancer · 2022Review
- Exploring the immunomodulatory role of virtual memory CD8Frontiers in immunology · 2022Article
- Lysine acetylation of NKG2D ligand Rae-1 stabilizes the protein and sensitizes tumor cells to NKG2D immune surveillance.Cancer letters · 2021Article
- Down-regulation of immune checkpoints by doxorubicin and carboplatin-containing neoadjuvant regimens in a murine breast cancer model.Iranian journal of basic medical sciences · 2021Article
- Tyrosine Kinase Inhibitor Cabozantinib Inhibits Murine Renal Cancer by Activating Innate and Adaptive Immunity.Frontiers in oncology · 2021Article
- MICA enhances sensitivity to cisplatin in patients with extensive small cell lung cancer via downregulation of ABCG2.Oncology letters · 2020Article
- Immunology of IL-12: An update on functional activities and implications for disease.EXCLI journal · 2020Review
- Tumor-targeted IL-12 combined with tumor resection yields a survival-favorable immune profile.Journal for immunotherapy of cancer · 2019Article
- Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.PLoS pathogens · 2019Article
- T-cell Homing Therapy for Reducing Regulatory T Cells and Preserving Effector T-cell Function in Large Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models.Journal of immunology research · 2018Article
- Induction of NKG2D Ligands on Solid Tumors Requires Tumor-Specific CD8Cancer immunology research · 2017Article
- Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma.Journal of immunology research · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIncreased infiltration of CD8+T cells into tumors has a positive impact on survival. Our previous study showed that doxorubicin (Dox) plus interleukin-12 (IL-12) boosted the accumulation of CD8+T cells in tumors and had a greater antitumor effect than did either agent alone. The purpose of this study was to determine the impact of NKG2D expression on CD8+T cell infiltration and antitumor efficacy.
methodsTumor-bearing mice were administered Dox, IL-12 plasmid DNA, or both via intraperitoneal injection or intramuscular electroporation. The induction of NKG2D on CD8+T cells and other lymphocytes was analyzed via flow cytometry, and NKG2D-positive CD8+T cell-specific localization in tumors was determined by using immunofluorescence staining in various types of immune cell-depleted mice.
resultsThe combination of Dox plus IL-12 specifically increased expression of NKG2D in CD8+T cells but not in other types of immune cells, including NK cells, which naturally express NKG2D. This induced NKG2D expression in CD8+T cells was associated with increased accumulation of CD8+T cells in murine tumors. Administration of NKG2D-blocking antibody or CD8+T cell-depletion antibody abrogated the NKG2D+CD8+T cell detection in tumors, whereas administration of NK cell-depletion antibody had no effect. Increased NKG2D expression in CD8+T cells was associated with increased antitumor efficacy in vivo.
conclusionWe conclude that Dox plus IL-12 induces NKG2D in CD8+T cells in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillance. This discovery reveals a novel mechanism for how chemoimmunotherapy synergistically promotes T cell-mediated antitumor immune surveillance.
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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.