CD25-Treg-Depleting Antibodies Preserving IL-2 Signaling on Effector T Cells Enhance Effector Activation and Antitumor Immunity

Scientists demonstrated potent single-agent activity of anti-CD25 antibodies optimized to deplete Treg cells, while preserving IL-2-STAT5 signaling on effector T cells and show synergy with immune checkpoint blockade in vivo.
[Nature Cancer]
CD25-T reg -depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity | Nature Cancer. (n.d.). Retrieved November 17, 2020, from https://www.nature.com/articles/s43018-020-00133-0 Cite
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SYK Inhibition Targets Acute Myeloid Leukemia Stem Cells by Blocking their Oxidative Metabolism

Investigators addressed the consequences of spleen tyrosine kinase (SYK) inhibition to leukemia stem-cell function and assessed SYK-associated pathways in acute myeloid leukemia cell biology.
[Cell Death & Disease]
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Persistent STAT5 Activation Reprograms the Epigenetic Landscape in CD4+ T Cells to Drive Polyfunctionality and Antitumor Immunity

Researchers report that persistent activation of signal transducer and activator of transcription 5 in tumor-specific CD4+ T cells drives the development of polyfunctional T cells.
[Science Immunology]
Ding, Z.-C., Shi, H., Aboelella, N. S., Fesenkova, K., Park, E.-J., Liu, Z., Pei, L., Li, J., McIndoe, R. A., Xu, H., Piazza, G. A., Blazar, B. R., Munn, D. H., & Zhou, G. (2020). Persistent STAT5 activation reprograms the epigenetic landscape in CD4+ T cells to drive polyfunctionality and antitumor immunity. Science Immunology, 5(52). https://doi.org/10.1126/sciimmunol.aba5962 Cite
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Antileukemic Activity of the VPS34-IN1 Inhibitor in Acute Myeloid Leukemia

Using a recently developed specific inhibitor, the authors found that vacuolar protein sorting 34 inhibition induces apoptosis in acute myeloid leukemia cells but not in normal CD34+ hematopoietic cells.
[Oncogenesis]
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STAT5 Promotes Accessibility and Is Required for BATF-Mediated Plasticity at the Il9 Locus

Scientists showed that STAT5 was the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures.
[Nature Communications]
STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus | Nature Communications. (n.d.). Retrieved September 28, 2020, from https://www.nature.com/articles/s41467-020-18648-6 Cite
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IL‐2/IL‐7‐Inducible Factors Pioneer the Path to T Cell Differentiation in Advance of Lineage‐Defining Factors

Scientists showed that IL‐2 signaling was required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus‐dependent alternative pathways of T cell differentiation.
[EMBO Journal]
AbstractGraphical Abstract
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Cancer SLC43A2 Alters T Cell Methionine Metabolism and Histone Methylation

Mechanistically, tumor cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter SLC43A2.
[Nature]
Bian, Y., Li, W., Kremer, D. M., Sajjakulnukit, P., Li, S., Crespo, J., Nwosu, Z. C., Zhang, L., Czerwonka, A., Pawłowska, A., Xia, H., Li, J., Liao, P., Yu, J., Vatan, L., Szeliga, W., Wei, S., Grove, S., Liu, J. R., … Zou, W. (2020). Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature, 1–6. https://doi.org/10.1038/s41586-020-2682-1 Cite
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10,11-Dehydrocurvularin Exerts Antitumor Effect against Human Breast Cancer by Suppressing STAT3 Activation

Scientists showed that 10,11-dehydrocurvularin (2–8 μM) dose-dependently inhibited the proliferation, migration and invasion of human breast cancer cell lines MDA-MB-231 and MDA-MB-468, and induced cell apoptosis.
[acta pharmacologica sinica]
Zhao, Q., Bi, Y., Zhong, J., Li, X., Guo, J., Liu, Y., Pan, L., Tan, Y., Deng, Z., & Yu, X. (2020). 10,11-dehydrocurvularin exerts antitumor effect against human breast cancer by suppressing STAT3 activation. Acta Pharmacologica Sinica, 1–10. https://doi.org/10.1038/s41401-020-0499-y Cite
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Assessment of STAT5 as a Potential Therapy Target in Enzalutamide-Resistant Prostate Cancer

Isobologram analysis revealed that the signal transducer and activator of transcription (STAT) 5 inhibitor pimozide combined with enzalutamide had additive and synergistic inhibitory effects on cell viability in the used models.
[PLoS One]
Erb, H. H. H., Bodenbender, J., Handle, F., Diehl, T., Donix, L., Tsaur, I., Gleave, M., Haferkamp, A., Huber, J., Fuessel, S., Juengel, E., Culig, Z., & Thomas, C. (2020). Assessment of STAT5 as a potential therapy target in enzalutamide-resistant prostate cancer. PLOS ONE, 15(8), e0237248. https://doi.org/10.1371/journal.pone.0237248 Cite
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Signaling Input from Divergent Pathways Subverts B Cell Transformation

The authors analyzed 1,148 patient-derived B-cell leukemia samples, and found that individual mutations did not promote leukemogenesis unless they converged on one single oncogenic pathway that was characteristic of the differentiation stage of transformed B cells.
[Nature]
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