Physioxia Enhances T Cell Development Ex Vivo from Human Hematopoietic Stem and Progenitor Cells

Investigators report that physiologically relevant oxygen concentration, an important environmental thymic factor promotes differentiation of cord blood CD34+ cells into progenitor T cells in serum‐free and feeder‐free culture system.
[Stem Cells]
Shin, D., Huang, X., Gil, C.-H., Aljoufi, A., Ropa, J., & Broxmeyer, H. E. (n.d.). Physioxia enhances T cell development ex vivo from human hematopoietic stem and progenitor cells. STEM CELLS, n/a(n/a). https://doi.org/10.1002/stem.3259 Cite
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A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in Patients with Classical Hodgkin Lymphoma

Investigators utilized the complementary approaches of T cell receptor sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 Phase II clinical trial
[Nature Medicine]
Cader, F. Z., Hu, X., Goh, W. L., Wienand, K., Ouyang, J., Mandato, E., Redd, R., Lawton, L. N., Chen, P.-H., Weirather, J. L., Schackmann, R. C. J., Li, B., Ma, W., Armand, P., Rodig, S. J., Neuberg, D., Liu, X. S., & Shipp, M. A. (2020). A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-020-1006-1 Cite
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Targeting Tumor‐Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies

Investigators propose a new vaccine platform that enhances all three arms of the adaptive immune system to improve tumor‐associated antigens‐based cancer vaccination in hepatocellular carcinoma patients.
[Hepatology]
Lu, L., Jiang, J., Zhan, M., Zhang, H., Wang, Q.-T., Sun, S.-N., Guo, X.-K., Yin, H., Wei, Y., Li, S.-Y., Liu, J. O., Li, Y., & He, Y.-W. (n.d.). Targeting Tumor-Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies. Hepatology, n/a(n/a). https://doi.org/10.1002/hep.31502 Cite
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Comprehensive Analyses of B Cell Compartments across the Human Body Reveal Novel Subsets and a Gut Resident Memory Phenotype

Data sets revealed that B cells in the blood were not in homeostasis with compartments in other tissues. Investigators found striking donor-to-donor variability in the frequencies and isotype of CD27+ memory B cells
[Blood]
Weisel, N. M., Weisel, F. J., Farber, D. L., Borghesi, L., Shen, Y., Ma, W., Luning Prak, E. T., & Shlomchik, M. (n.d.). Comprehensive analyses of B cell compartments across the human body reveal novel subsets and a gut resident memory phenotype. Blood. https://doi.org/10.1182/blood.2019002782 Cite
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Antitumour Dendritic Cell Vaccination in a Priming and Boosting Approach

The authors believe that currently available strategies for vaccines that target dendritic cells or use them to present antitumour antigens could be integrated into existing clinical practice using prime–boost approaches.
[Nature Reviews Drug Discovery]
Harari, A., Graciotti, M., Bassani-Sternberg, M., & Kandalaft, L. E. (2020). Antitumour dendritic cell vaccination in a priming and boosting approach. Nature Reviews Drug Discovery, 1–18. https://doi.org/10.1038/s41573-020-0074-8 Cite
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Mitochondrial DNA Enhance Innate Immune Responses in Neuromyelitis Optica by Monocyte Recruitment and Activation

Investigators established anti-AQP4 recombinant autoantibodies from plasmablasts in neuromyelitis optica spectrum disorder patient’s cereberospinal fluid.
[Scientific Reports]
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Myeloid-Derived Suppressor Cell Depletion Therapy Targets IL-17A-Expressing Mammary Carcinomas

Investigators report here that IL-17A mRNA and protein were detectable in some human triple-negative breast cancer cell lines and further upregulated by IL-23 and LPS stimulation.
[Scientific Reports]
Dawod, B., Liu, J., Gebremeskel, S., Yan, C., Sappong, A., Johnston, B., Hoskin, D. W., Marshall, J. S., & Wang, J. (2020). Myeloid-derived suppressor cell depletion therapy targets IL-17A-expressing mammary carcinomas. Scientific Reports, 10(1), 13343. https://doi.org/10.1038/s41598-020-70231-7 Cite
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Reversal of Pre-existing NGFR-Driven Tumor and Immune Therapy Resistance

Researchers chronically exposed patient-derived melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observed strong enrichment of a pre-existing NGFRhi population.
[Nature Communications]
Boshuizen, J., Vredevoogd, D. W., Krijgsman, O., Ligtenberg, M. A., Blankenstein, S., de Bruijn, B., Frederick, D. T., Kenski, J. C. N., Parren, M., Brüggemann, M., Madu, M. F., Rozeman, E. A., Song, J.-Y., Horlings, H. M., Blank, C. U., van Akkooi, A. C. J., Flaherty, K. T., Boland, G. M., & Peeper, D. S. (2020). Reversal of pre-existing NGFR-driven tumor and immune therapy resistance. Nature Communications, 11(1), 3946. https://doi.org/10.1038/s41467-020-17739-8 Cite
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Prostaglandin E2 Stimulates cAMP Signaling and Re-Sensitizes Human Leukemia Cells to Glucocorticoid-Induced Cell Death

To identify glucocorticoid resistance pathways, investigators conducted a genome-wide, survival-based, shRNA screen in murine T cell acute lymphoblastic leukemia cells.
[Blood]
Roderick, J. E., Gallagher, K. M., Murphy, L. C., O’Connor, K. W., Tang, K., Zhang, B., Brehm, M., Greiner, D. L., Yu, J., Zhu, L. J., Green, M. R., & Kelliher, M. A. (n.d.). Prostaglandin E2 stimulates cAMP signaling and re-sensitizes human leukemia cells to glucocorticoid-induced cell death. Blood. https://doi.org/10.1182/blood.2020005712 Cite
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EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma

Scientists report that Eph receptor A5 (EPHA5) mutations were associated with increased tumor mutation burden, neoantigen load, levels of immune-related gene expression signatures, and enhanced tumor-infiltrating lymphocytes in lung adenocarcinoma.
[Cancer Gene Therapy]
Huang, W., Lin, A., Luo, P., Liu, Y., Xu, W., Zhu, W., Wei, T., Lyu, Q., Guo, L., & Zhang, J. (2020). EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma. Cancer Gene Therapy, 1–11. https://doi.org/10.1038/s41417-020-0207-6 Cite
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Chromatin Accessibility Landscape of Pediatric T-Lymphoblastic Leukemia and Human T-Cell Precursors

Developmental stages were distinguished by 2,823 signature chromatin regions with 95% accuracy. Open chromatin surrounding SAE 1 was identified to best distinguish thymic developmental stages suggesting a potential role of SUMO ylation in T‐cell development.
[EMBO Molecular Medicine]
Erarslan-Uysal, B., Kunz, J. B., Rausch, T., Richter-Pechańska, P., van Belzen, I. A., Frismantas, V., Bornhauser, B., Ordoñez-Rueada, D., Paulsen, M., Benes, V., Stanulla, M., Schrappe, M., Cario, G., Escherich, G., Bakharevich, K., Kirschner-Schwabe, R., Eckert, C., Loukanov, T., Gorenflo, M., … Kulozik, A. E. (2020). Chromatin accessibility landscape of pediatric T-lymphoblastic leukemia and human T-cell precursors. EMBO Molecular Medicine, n/a(n/a), e12104. https://doi.org/10.15252/emmm.202012104 Cite
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Immunostimulation with Chemotherapy in the Era of Immune Checkpoint Inhibitors

Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors relative to their effectiveness as monotherapies.
[Nature Reviews Clinical Oncology]
Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020). Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nature Reviews Clinical Oncology, 1–17. https://doi.org/10.1038/s41571-020-0413-z Cite
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