A Distal Foxp3 Enhancer Enables Interleukin-2 Dependent Thymic Treg Cell Lineage Commitment for Robust Immune Tolerance

The authors report that IL-2 – STAT5 signaling converged on an enhancer during Foxp3 induction.
[Immunity]
Dikiy, S., Li, J., Bai, L., Jiang, M., Janke, L., Zong, X., Hao, X., Hoyos, B., Wang, Z.-M., Xu, B., Fan, Y., Rudensky, A. Y., & Feng, Y. (2021). A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.03.020 Cite
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A Selective HDAC8 Inhibitor Potentiates Antitumor Immunity and Efficacy of Immune Checkpoint Blockade in Hepatocellular Carcinoma

The authors demonstrated that selective HDAC8 inhibition elicited effective and durable responses to immune-checkpoint blockade by co-opting adaptive immunity through enhancer reprogramming.
[Science Translational Medicine]
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Single-Cell Analysis of FOXP3 Deficiencies in Humans and Mice Unmasks Intrinsic and Extrinsic CD4+ T Cell Perturbations

CD4+ T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous Treg-like cells, some very similar to normal Treg cells, others more distant.
[Nature Immunology]
Zemmour, D., Charbonnier, L.-M., Leon, J., Six, E., Keles, S., Delville, M., Benamar, M., Baris, S., Zuber, J., Chen, K., Neven, B., Garcia-Lloret, M. I., Ruemmele, F. M., Brugnara, C., Cerf-Bensussan, N., Rieux-Laucat, F., Cavazzana, M., André, I., Chatila, T. A., … Benoist, C. (2021). Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4 + T cell perturbations. Nature Immunology, 1–13. https://doi.org/10.1038/s41590-021-00910-8 Cite
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Prognostic and Therapeutic Implications of Extracellular Matrix Associated Gene Signature in Renal Clear Cell Carcinoma

The expression of ECM-related genes was explored for prognostic and immunological implication in clear cell renal clear cell carcinoma.
[Scientific Reports]
Ahluwalia, P., Ahluwalia, M., Mondal, A. K., Sahajpal, N., Kota, V., Rojiani, M. V., Rojiani, A. M., & Kolhe, R. (2021). Prognostic and therapeutic implications of extracellular matrix associated gene signature in renal clear cell carcinoma. Scientific Reports, 11(1), 7561. https://doi.org/10.1038/s41598-021-86888-7 Cite
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Metabolic Modulation by CDK4/6 Inhibitor Promotes Chemokine-Mediated Recruitment of T Cells Into Mammary Tumors

Investigators showed that cyclin-dependent kinases 4 and 6 (CDK4/6i) could enhance efficacy of T cell-based therapies, such as adoptive T cell transfer or T cell-activating antibodies anti-OX40/anti-4-1BB, in murine breast cancer models.
[Cell Reports]
Uzhachenko, R. V., Bharti, V., Ouyang, Z., Blevins, A., Mont, S., Saleh, N., Lawrence, H. A., Shen, C., Chen, S.-C., Ayers, G. D., DeNardo, D. G., Arteaga, C., Richmond, A., & Vilgelm, A. E. (2021). Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors. Cell Reports, 35(1). https://doi.org/10.1016/j.celrep.2021.108944 Cite
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How to Turn Up the Heat on the Cold Immune Microenvironment of Metastatic Prostate Cancer

The authors discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies.
[Prostate Cancer and Prostatic Diseases]
Stultz, J., & Fong, L. (2021). How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer. Prostate Cancer and Prostatic Diseases, 1–21. https://doi.org/10.1038/s41391-021-00340-5 Cite
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Small Extracellular Vesicles Derived from Interferon-γ Pre-Conditioned Mesenchymal Stromal Cells Effectively Treat Liver Fibrosis

Investigators analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs).
[NPJ Regenerative Medicine]
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Reprogramming Lipid Metabolism Prevents Effector T Cell Senescence and Enhances Tumor Immunotherapy

Researchers report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers
[Science Translational Medicine]
Liu, X., Hartman, C. L., Li, L., Albert, C. J., Si, F., Gao, A., Huang, L., Zhao, Y., Lin, W., Hsueh, E. C., Shen, L., Shao, Q., Hoft, D. F., Ford, D. A., & Peng, G. (2021). Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy. Science Translational Medicine, 13(587). https://doi.org/10.1126/scitranslmed.aaz6314 Cite
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A Tumor-Specific Mechanism of Treg Enrichment Mediated by the Integrin αvβ8

Researchers describe a mechanism for Treg enrichment in mouse and human tumors mediated by the αvβ8 integrin.
[Science Immunology]
Seed, R. I., Kobayashi, K., Ito, S., Takasaka, N., Cormier, A., Jespersen, J. M., Publicover, J., Trilok, S., Combes, A. J., Chew, N. W., Chapman, J., Krummel, M. F., Lou, J., Marks, J., Cheng, Y., Baron, J. L., & Nishimura, S. L. (2021). A tumor-specific mechanism of Treg enrichment mediated by the integrin αvβ8. Science Immunology, 6(57). https://doi.org/10.1126/sciimmunol.abf0558 Cite
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Regulatory T Cells in Ischemic Stroke

Scientists describe how Treg cells fluctuate and play a role in the regulation of immune responses after ischemic stroke in both experimental animals and humans, and summarize their biological functions and mechanisms in both CNS and periphery.
[Acta Pharmacologica Sinica]
Wang, H., Ye, J., Cui, L., Chu, S., & Chen, N. (2021). Regulatory T cells in ischemic stroke. Acta Pharmacologica Sinica, 1–9. https://doi.org/10.1038/s41401-021-00641-4 Cite
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Tissue Regulatory T Cells: Regulatory Chameleons

The deepening knowledge of tissue Treg cell biology will inform ongoing attempts to harness Treg cells for precision immunotherapeutics.
[Nature Reviews Immunology]
Muñoz-Rojas, A. R., & Mathis, D. (2021). Tissue regulatory T cells: regulatory chameleons. Nature Reviews Immunology, 1–15. https://doi.org/10.1038/s41577-021-00519-w Cite
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