Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models

Researchers generated and characterized traceable CAR T cells and examined potential negative effects of radionuclide reporter use. They applied the platform to two different triple-negative breast cancer models and unexpectedly observed pronounced differences in CAR-T tumor retention by PET/computed tomography and confirmed data ex vivo.
[Molecular Therapy]
Volpe, A., Lang, C., Lim, L., Man, F., Kurtys, E., Ashmore-Harris, C., Johnson, P., Skourti, E., Rosales, R. T. M. de, & Fruhwirth, G. O. (2020). Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2020.06.028 Cite
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Regulatory T Cells Suppress Th17 Cell Ca2+ Signaling in the Spinal Cord during Murine Autoimmune Neuroinflammation

Investigators used two-photon microscopy to elucidate the spatial organization, motility characteristics, and interactions of endogenous Treg and Th17 cells together with antigen-presenting cells within the spinal cord leptomeninges in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.
[Proceedings of the National Academy of Sciences of the United States of America]
Othy, S., Jairaman, A., Dynes, J. L., Dong, T. X., Tune, C., Yeromin, A. V., Zavala, A., Akunwafo, C., Chen, F., Parker, I., & Cahalan, M. D. (2020). Regulatory T cells suppress Th17 cell Ca2+ signaling in the spinal cord during murine autoimmune neuroinflammation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2006895117 Cite
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Specific Targeting of Ovarian Tumor-Associated Macrophages by Large, Anionic Nanoparticles

Researchers showed that relatively large anionic nanoparticles administered intraperitoneally selectively accumulated in tumor-associated macrophages.
[Proceedings of the National Academy of Sciences of the United States of America]
Haber, T., Cornejo, Y. R., Aramburo, S., Flores, L., Cao, P., Liu, A., Mooney, R., Gilchrist, M., Tirughana, R., Nwokafor, U., Abidi, W., Han, E., Dellinger, T., Wakabayashi, M. T., Aboody, K. S., & Berlin, J. M. (2020). Specific targeting of ovarian tumor-associated macrophages by large, anionic nanoparticles. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1917424117 Cite
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Microbiota-Dependent Expansion of Testicular IL-17-Producing Vγ6+ γδ T Cells upon Puberty Promotes Local Tissue Immune Surveillance

Investigators characterized a population of interleukin 17-producing γδ T cells that seeded the testis of naive C57BL/6 mice, expand at puberty and persisted throughout adulthood.
[Mucosal Immunology]
Wilharm, A., Brigas, H. C., Sandrock, I., Ribeiro, M., Amado, T., Reinhardt, A., Demera, A., Hoenicke, L., Strowig, T., Carvalho, T., Prinz, I., & Ribot, J. C. (2020). Microbiota-dependent expansion of testicular IL-17-producing Vγ6 + γδ T cells upon puberty promotes local tissue immune surveillance. Mucosal Immunology, 1–11. https://doi.org/10.1038/s41385-020-0330-6 Cite
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Histone Deacetylase 3 Controls Lung Alveolar Macrophage Development and Homeostasis

Researchers showed that histone deacetylase 3 was a key epigenetic factor required for avelolar macrophage embryonic development, postnatal homeostasis, maturation, and regeneration from bone marrow.
[Nature Communications]
Yao, Y., Liu, Q., Adrianto, I., Wu, X., Glassbrook, J., Khalasawi, N., Yin, C., Yi, Q., Dong, Z., Geissmann, F., Zhou, L., & Mi, Q.-S. (2020). Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis. Nature Communications, 11(1), 3822. https://doi.org/10.1038/s41467-020-17630-6 Cite
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Strategic Alliance a Shot in the Arm for Stem Cell Commercialization Efforts

Several Canadian-made cell therapies will take a major step closer to the clinic thanks to a new collaboration between the Ontario Institute for Regenerative Medicine and the Centre for Commercialization of Cancer Immunotherapy and Regenerative Medicine.
[Ontario Institute for Regenerative Medicine]
Press Release

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The Cytokine Receptor IL-7Rα Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3+ Treg Cells

Researchers report that IL-7Rα downregulation was necessary to maximize IL-2R signaling. While IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells.
[iScience]
Waickman, A. T., Keller, H. R., Kim, T.-H., Luckey, M. A., Tai, X., Hong, C., Molina-Paris, C., Walsh, S. T. R., & Park, J.-H. (2020). The cytokine receptor IL-7Rα impairs IL-2 receptor signaling and constrains the in vitro differentiation of Foxp3+ Treg cells. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101421 Cite
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PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells

Scientists found that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15.
[Cell Reports]
Flosbach, M., Oberle, S. G., Scherer, S., Zecha, J., Hoesslin, M. von, Wiede, F., Chennupati, V., Cullen, J. G., List, M., Pauling, J. K., Baumbach, J., Kuster, B., Tiganis, T., & Zehn, D. (2020). PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells. Cell Reports, 32(4). https://doi.org/10.1016/j.celrep.2020.107957 Cite
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An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages

The authors showed that independently of GSDMD-mediated plasma membrane permeabilization, inflammasome receptors engaged caspase-1 and caspase-8, both of which redundantly promoted activation of apoptotic executioner caspase-3 and caspase-7 in pyroptotic macrophages.
[Cell Reports]
Vasconcelos, N. M. de, Opdenbosch, N. V., Gorp, H. V., Martín-Pérez, R., Zecchin, A., Vandenabeele, P., & Lamkanfi, M. (2020). An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages. Cell Reports, 32(4). https://doi.org/10.1016/j.celrep.2020.107959 Cite
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Control of Viral Infection by Natural Killer Cell Inhibitory Receptors

Investigators showed MHC-I-restricted control of murine cytomegalovirus (MCMV) infection in vivo that was NK cell dependent. Using mice lacking specific Ly49 receptors, they showed that control of MCMV required inhibitory Ly49 receptors and an inhibitory signaling motif and the capacity for MCMV to downregulate MHC-I.
[Cell Reports]
Parikh, B. A., Bern, M. D., Piersma, S. J., Yang, L., Beckman, D. L., Poursine-Laurent, J., Plougastel-Douglas, B., & Yokoyama, W. M. (2020). Control of Viral Infection by Natural Killer Cell Inhibitory Receptors. Cell Reports, 32(4). https://doi.org/10.1016/j.celrep.2020.107969 Cite
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CD122-Targetted IL-2 Signals Cause Acute and Selective Apoptosis of B Cells in Peyer’s Patches

Scientists found that IL-2C targeting cells expressing IL-2 receptor beta caused an acute decrease in cellularity of Peyer’s Patches while cell numbers in the lamina propria and intraepithelial lymphocytes were unaffected.
[Scientific Reports]
Singh, A., Dhume, K., Tejero, J. D., Strutt, T. M., & McKinstry, K. K. (2020). CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer’s Patches. Scientific Reports, 10(1), 12668. https://doi.org/10.1038/s41598-020-69632-5 Cite
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The Soluble Glycoprotein NMB (GPNMB) Produced by Macrophages Induces Cancer Stemness and Metastasis via CD44 and IL-33

Using mouse tumor models, the authors showed that macrophage-derived soluble glycoprotein nonmetastatic B (GPNMB) increased tumor growth and metastasis in Gpnmb-mutant mice.
[Cellular & Molecular Immunology]
Liguori, M., Digifico, E., Vacchini, A., Avigni, R., Colombo, F. S., Borroni, E. M., Farina, F. M., Milanesi, S., Castagna, A., Mannarino, L., Craparotta, I., Marchini, S., Erba, E., Panini, N., Tamborini, M., Rimoldi, V., Allavena, P., & Belgiovine, C. (2020). The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33. Cellular & Molecular Immunology, 1–12. https://doi.org/10.1038/s41423-020-0501-0 Cite
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