ArticleCancer research2016
Efficacy of Adoptive T-cell Therapy Is Improved by Treatment with the Antioxidant N-Acetyl Cysteine, Which Limits Activation-Induced T-cell Death.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Differential Radiosensitivity in T-Cell Subsets: Metabolic and Antioxidative Mechanisms Underlying Naïve T-Cell Vulnerability.Radiation research · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Effects of functional antioxidants on the expansion of gamma delta T-cells and their cellular cytotoxicity against bladder cancer cells.BMC cancer · 2025Article
- N-acetylcysteine stimulates organelle malfunction in endometriotic cells via IFN-gamma signaling.Scientific reports · 2025Article
- Alginate-based artificial antigen presenting cells expand functional CD8Biomaterials · 2025Article
- Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.Nature biomedical engineering · 2024Article
- Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.International journal of molecular sciences · 2024Review
- Acetylcysteine synergizes PD-1 blockers against colorectal cancer progression by promoting TCF1Cell communication and signaling : CCS · 2024Article
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- A metabolic perspective on nitric oxide function in melanoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Exploring the causal relationship between gut microbiota and multiple myeloma risk based on Mendelian randomization and biological annotation.Frontiers in microbiology · 2024Article
- Antiproliferative effects of mitochondria-targeted N-acetylcysteine and analogs in cancer cells.Scientific reports · 2023Article
- Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches.Biomarker research · 2023Review
- NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.Redox biology · 2022Review
- Dual near-infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Yttrium chloride-induced cytotoxicity and DNA damage response via ROS generation and inhibition of Nrf2/PPARγ pathways in H9c2 cardiomyocytes.Archives of toxicology · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Although adoptive transfer of autologous tumor antigen-specific T-cell immunotherapy can produce remarkable clinical efficacy, most patients do not achieve durable complete responses. We hypothesized that reducing susceptibility of T cells to activation-induced cell death (AICD), which increases during the rapid in vitro expansion of therapeutic T cells before their infusion, might improve the persistence of adoptively transferred cells. Our investigations revealed that repetitive stimulation of the T-cell receptor (TCR) induced AICD, as a result of activating the DNA damage response pathway through ATM-mediated Ser15 phosphorylation of p53. Activation of this DNA damage response pathway also occurred upon antigen-specific restimulation in TCR-transduced TIL1383I T cells prepared for adoptive transfer to patients as part of a clinical trial. Notably, treatment with the antioxidant N-acetyl cysteine (NAC) significantly reduced upregulation of the DNA damage marker γH2AX, subsequent ATM activation, and cell death. In the Pmel mouse model of melanoma, the presence of NAC during ex vivo T-cell expansion improved the persistence of adoptively transferred cells, reduced tumor growth, and increased survival. Taken together, our results offer a preclinical proof of concept for the addition of NAC to current therapeutic T-cell expansion protocols, offering immediate potential to improve the quality and therapeutic efficacy of adoptive T-cell therapeutics infused into patients. Cancer Res; 76(20); 6006-16. ©2016 AACR.
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