ArticleCancer immunology, immunotherapy : CII2018
N-acetyl cysteine protects anti-melanoma cytotoxic T cells from exhaustion induced by rapid expansion via the downmodulation of Foxo1 in an Akt-dependent manner.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Immune regeneration: implications for cancer immunotherapy and beyond.The Journal of clinical investigation · 2025Review
- Effects of functional antioxidants on the expansion of gamma delta T-cells and their cellular cytotoxicity against bladder cancer cells.BMC cancer · 2025Article
- Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy.Aging cell · 2025Review
- N-acetylcysteine stimulates organelle malfunction in endometriotic cells via IFN-gamma signaling.Scientific reports · 2025Article
- N-Acetyl Cysteine as a promising therapeutic approach in ovarian cancer: potential and perspectives.Academia oncology · 2025Article
- The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death.Cellular & molecular biology letters · 2024Review
- Acetylcysteine synergizes PD-1 blockers against colorectal cancer progression by promoting TCF1Cell communication and signaling : CCS · 2024Article
- Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.Journal for immunotherapy of cancer · 2024Article
- Metabolic waypoints during T cell differentiation.Nature immunology · 2024Review
- Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.Science advances · 2024Article
- CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.Nature reviews. Clinical oncology · 2024Review
- Antiproliferative effects of mitochondria-targeted N-acetylcysteine and analogs in cancer cells.Scientific reports · 2023Article
- Metabolic Regulation of T cell Activity: Implications for Metabolic-Based T-cell Therapies for CancerIranian biomedical journal · 2023Review
- NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.Redox biology · 2022Review
- FoxO Transcription Factors: Applicability as a Novel Immune Cell Regulators and Therapeutic Targets in Oxidative Stress-Related Diseases.International journal of molecular sciences · 2022Review
- Melanocytotoxic chemicals and their toxic mechanisms.Toxicological research · 2022Review
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Here, we show that these benefits of NAC can be extended to engineered T cells and significantly increases T-cell survival within the tumor microenvironment. The addition of NAC to the expansion protocol of human TIL13838I TCR-transduced T cells that are under evaluation in a Phase I clinical trial, demonstrated that findings in murine cells extend to human cells. Expansion of TIL13838I TCR-transduced T cells in NAC also increased their ability to kill target cells in vitro. Interestingly, NAC did not affect memory subsets, but diminished up-regulation of senescence (CD57) and exhaustion (PD-1) markers and significantly decreased expression of the transcription factors EOMES and Foxo1. Pharmacological inhibition of the PI3K/Akt pathway ablates the decrease in Foxo1 induced by NAC treatment of activated T cells. This suggests a model in which NAC through PI3K/Akt activation suppresses Foxo1 expression, thereby impacting its transcriptional targets EOMES, PD-1, and granzyme B. Taken together, our results indicate that NAC exerts pleiotropic effects that impact the quality of TCR-transduced T cells and suggest that the addition of NAC to current clinical protocols should be considered.
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