Tumor-Infiltrating Mast Cells Are Associated With Resistance to Anti-PD-1 Therapy

Researchers generated a humanized-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull mice.
[Nature Communications]
Somasundaram, R., Connelly, T., Choi, R., Choi, H., Samarkina, A., Li, L., Gregorio, E., Chen, Y., Thakur, R., Abdel-Mohsen, M., Beqiri, M., Kiernan, M., Perego, M., Wang, F., Xiao, M., Brafford, P., Yang, X., Xu, X., Secreto, A., … Herlyn, M. (2021). Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. Nature Communications, 12(1), 346. https://doi.org/10.1038/s41467-020-20600-7 Cite
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Efficient IL-2R Signaling Differentially affects the Stability, Function, and Composition of the Regulatory T-Cell Pool

Investigators characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling.
[Cellular & Molecular Immunology]
Permanyer, M., Bošnjak, B., Glage, S., Friedrichsen, M., Floess, S., Huehn, J., Patzer, G. E., Odak, I., Eckert, N., Zargari, R., Ospina-Quintero, L., Georgiev, H., & Förster, R. (2021). Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool. Cellular & Molecular Immunology, 1–17. https://doi.org/10.1038/s41423-020-00599-z Cite
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A Noninflammatory mRNA Vaccine for Treatment of Experimental Autoimmune Encephalomyelitis

Scientists showed that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals.
[Science]
Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., Diken, M., Kreiter, S., Yogev, N., Waisman, A., Karikó, K., Türeci, Ö., & Sahin, U. (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, 371(6525), 145–153. https://doi.org/10.1126/science.aay3638 Cite
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Platelet-Targeted Gene Therapy Induces Robust Immune Tolerance Even in a Primed Model via Peripheral Clonal Deletion of Antigen-Specific CD4 and CD8 T Cells and Expansion of Antigen-Specific Regulatory T Cells

Using the OT-I/WT model, we showed that antigen-specific CD8 T cells were partially deleted in recipients after platelet-targeted gene transfer.
[Molecular Therapy-Nucleic Acids]
Li, J., Chen, J., Schroeder, J. A., Hu, J., Williams, C. B., & Shi, Q. (2021). Platelet-targeted gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific CD4 and CD8 T cells and expansion of antigen-specific regulatory T cells. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2020.12.026 Cite
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RANK Links Thymic Regulatory T Cells to Fetal Loss and Gestational Diabetes in Pregnancy

Investigators showed that the osteoclast differentiation receptor RANK couples female sex hormones to the rewiring of the thymus during pregnancy.
[Nature]
RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy | Nature. (n.d.). Retrieved January 5, 2021, from https://www.nature.com/articles/s41586-020-03071-0 Cite
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Receptor-Gated IL-2 Delivery by an Anti-Human IL-2 Antibody Activates Regulatory T Cells in Three Different Species

Using a cell-based and dynamic IL-2R platform, researchers identified a particular anti-human IL-2 antibody, termed UFKA-20. When bound to UFKA-20, IL-2 failed to stimulate cells expressing IL-2Rβ and IL-2Rγ, unless these cells also expressed high amounts of CD25.
[Science Translational Medicine]
Karakus, U., Sahin, D., Mittl, P. R. E., Mooij, P., Koopman, G., & Boyman, O. (2020). Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species. Science Translational Medicine, 12(574). https://doi.org/10.1126/scitranslmed.abb9283 Cite
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Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid Cells

Researchers demonstrated that regulatory T cell ablation-dependent anti-tumor effects in murine breast cancer required intratumoral recruitment of CCR2+ inflammatory monocytes, which primarily differentiated into tumor-associated macrophages, and led to reprogramming of their function in an IFN-γ-dependent manner.
[Cell Reports]
Clark, N. M., Martinez, L. M., Murdock, S., deLigio, J. T., Olex, A. L., Effi, C., Dozmorov, M. G., & Bos, P. D. (2020). Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid Cells. Cell Reports, 33(10). https://doi.org/10.1016/j.celrep.2020.108482 Cite
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Orally Desensitized Mast Cells Form a Regulatory Network with Treg Cells for the Control of Food Allergy

To elucidate the mechanisms of oral immunotherapy (OIT), especially during the immunological transition from desensitization to allergy regulation, researchers generated a clinical OIT murine model and used it to examine immunological events of OIT.
[Mucosal Immunology]
Takasato, Y., Kurashima, Y., Kiuchi, M., Hirahara, K., Murasaki, S., Arai, F., Izawa, K., Kaitani, A., Shimada, K., Saito, Y., Toyoshima, S., Nakamura, M., Fujisawa, K., Okayama, Y., Kunisawa, J., Kubo, M., Takemura, N., Uematsu, S., Akira, S., … Kiyono, H. (2020). Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy. Mucosal Immunology, 1–12. https://doi.org/10.1038/s41385-020-00358-3 Cite
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Cross Talk between Human Regulatory T Cells and Antigen Presenting Cells: Lessons for Clinical Applications

Scientists focus on the roles of antigen presenting cells (APCs) in the generation and function of Tregs in humans. In addition to stimulating the development of Tregs, APCs activate Tregs and provide signals that induce specialised functional and homing marker expression.
[European Journal of Immunology]
Wardell, C. M., MacDonald, K. N., Levings, M. K., & Cook, L. (n.d.). Cross talk between human regulatory T cells and antigen presenting cells: Lessons for clinical applications. European Journal of Immunology, n/a(n/a). https://doi.org/https://doi.org/10.1002/eji.202048746 Cite
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Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

Functional characterization of intratumoral Tregs was performed by a proliferation assay using FACS-sorted Tregs as suppressor cells and autologous CellTrace Violet-labelled T effector cells as responder cells.
[Blood]
Spasevska, I., Josefsson, S., Blaker, Y. N., Steen, C. B., Sharma, A., Kushekhar, K., Meyer, S., Kolstad, A., Beiske, K., Holte, H., Østenstad, B., Kimby, E., Olweus, J., Tasken, K., Lorenz, S., Smeland, E. B., Alizadeh, A. A., Huse, K., & Myklebust, J. H. (2020). Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma. Blood, 136(Supplement 1), 27–28. https://doi.org/10.1182/blood-2020-142380 Cite
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Identification of Regulatory T Cell Molecules Associated with Severity of Multiple Sclerosis

Scientists determined whether the expression of functionally relevant TGF-β-regulated molecules was altered in Tregs from patients with multiple sclerosis.
[Multiple Sclerosis Journal]
Identification of regulatory T cell molecules associated with severity of multiple sclerosis - MA Tapia-Maltos, I Treviño-Frenk, HB García-González, M Rosetti, V Barriga-Maldonado, F Morales-Ramírez, DC López-Hernández, F Rosetti, JC Crispín, 2020. (n.d.). Retrieved December 15, 2020, from https://journals.sagepub.com/doi/abs/10.1177/1352458520977045 Cite
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