ArticleScientific reports2022
Direct AKT activation in tumor-infiltrating lymphocytes markedly increases interferon-γ (IFN-γ) for the regression of tumors resistant to PD-1 checkpoint blockade.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Nuclear translocation of mitochondrial ferredoxin reductase is regulated by AKT-mediated phosphorylation.The Biochemical journal · 2026Article
- M1 Macrophage Extracellular Vesicles and TLR3 Agonist Nanoparticles Down-Regulate Immunosuppression and Metastasis via AKT/TAM in Triple-Negative Breast Cancer.Molecular carcinogenesis · 2025Article
- Cellular and molecular mechanisms of arenobufagin in cancer therapy: a systematic review.Discover oncology · 2025Review
- Immunometabolism of regulatory T cells in cancer.Oncogene · 2025Review
- Anti-PD-1 amplifies costimulation in melanoma-infiltrating TJournal for immunotherapy of cancer · 2025Article
- Protein Phosphatase 2A Promotes CD8Research (Washington, D.C.) · 2025Article
- Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro.International forum of allergy & rhinology · 2024Article
- Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients.British journal of cancer · 2024Article
- Effects of Akt Activator SC79 on Human M0 Macrophage Phagocytosis and Cytokine Production.Cells · 2024Article
- Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer.Molecular cancer · 2024Review
- A strategy to disentangle direct and indirect effects on (de)phosphorylation by chemical modulators of the phosphatase PP1 in complex cellular contexts.Chemical science · 2024Article
- Combining single-cell RNA sequencing and network pharmacology to explore the target of cangfu daotan decoction in the treatment of obese polycystic ovary syndrome from an immune perspective.Frontiers in pharmacology · 2024Article
- Review
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Authors and funding
5 authors at 3 institutions in 1 country.
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Abstract
PD-1 immune checkpoint blockade against inhibitory receptors such as receptor programmed cell death-1 (PD-1), has revolutionized cancer treatment. Effective immune reactivity against tumour antigens requires the infiltration and activation of tumour-infiltrating T-cells (TILs). In this context, ligation of the antigen-receptor complex (TCR) in combination with the co-receptor CD28 activates the intracellular mediator AKT (or PKB, protein kinase B) and its downstream targets. PD-1 inhibits the activation of AKT/PKB. Given this, we assessed whether the direct activation of AKT might be effective in activating the immune system to limit the growth of tumors that are resistant to PD-1 checkpoint blockade. We found that the small molecule activator of AKT (SC79) limited growth of a B16 tumor and an EMT-6 syngeneic breast tumor model that are poorly responsive to PD-1 immunotherapy. In the case of B16 tumors, direct AKT activation induced (i) a reduction of suppressor regulatory (Treg) TILs and (ii) an increase in effector CD8+ TILs. SC79 in vivo therapy caused a major increase in the numbers of CD4+ and CD8+ TILs to express interferon-γ (IFN-γ). This effect on IFN-γ expression distinguished responsive from non-responsive anti-tumor responses and could be recapitulated ex vivo with human T-cells. In CD4+FoxP3+Treg TILs, AKT induced IFN-γ expression was accompanied by a loss of suppressor activity, the conversation to CD4
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