Calcineurin Inhibitors Suppress Acute Graft-vs-Host Disease via NFAT-Independent Inhibition of T Cell Receptor Signaling

Researchers utilized T cells from mice that express LckS59A, which cannot accept a phosphate at residue 59, to initiate acute graft-versus-host disease.
[Journal of Clinical Investigation]
Otsuka, S., Melis, N., Gaida, M. M., Dutta, D., Weigert, R., & Ashwell, J. D. (2021). Calcineurin inhibitors suppress acute graft-vs-host disease via NFAT-independent inhibition of T cell receptor signaling. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI147683 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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Female Immunity Protects from Cutaneous Squamous Cell Carcinoma

Researchers presented data showing women presented less aggressive primary cutaneous squamous cell carcinoma and early strong immune activation.
[Clinical Cancer Research]
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Myeloid Cell–Derived HOCl Is a Paracrine Effector That Trans-inhibits IKK/NF-κB in Melanoma Cells and Limits Early Tumor Progression

Investigators revealed a role for myeloid-derived cells-derived hypochlorous acid (HOCl) as a small-molecule paracrine signaling factor that trans-inhibited inhibited IκB kinase (IKK) in melanoma tumor cells, mediating antitumor responses during early tumor progression.
[Science Signaling]
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Improving Outcomes in Chronic Myeloid Leukemia through Harnessing the Immunological Landscape

Scientists focus on immune dysfunction in newly diagnosed chronic myeloid leukemia patients, and the role that tyrosine kinase inhibitors and other therapies have in restoring immune surveillance.
[Leukemia]
Hsieh, Y.-C., Kirschner, K., & Copland, M. (2021). Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia, 1–14. https://doi.org/10.1038/s41375-021-01238-w 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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A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response.
[Molecular Therapy]
Alwis, R. de, Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Low, J. G. H., Kalimuddin, S., Matsuda, D., Allen, E. C., Hartman, P., Park, J., Alayyoubi, M., Bhaskaran, H., Dukanovic, A., Bao, Y., Clemente, B., Vega, J., … Ooi, E. E. (2021). A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.04.001 Cite
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Combining Ibrutinib and Checkpoint Blockade Improves CD8+ T-Cell Function and Control of Chronic Lymphocytic Leukemia in Em-TCL1 Mice

By using the Eµ-TCL1 adoptive transfer mouse model of chronic lymphocytic leukemia, scientists observed that ibrutinib effectively controled leukemia development, but also resulted in significantly lower numbers of CD8+ effector T-cells, with lower expression of activation markers, as well as impaired proliferation and effector function.
[Haematologica]
Hanna, B. S., Yazdanparast, H., Demerdash, Y., Roessner, P. M., Schulz, R., Lichter, P., Stilgenbauer, S., & Seiffert, M. (2021). Combining ibrutinib and checkpoint blockade improves CD8+ T-cell function and control of chronic lymphocytic leukemia in Em-TCL1 mice. Haematologica, 106(4), 968–977. https://doi.org/10.3324/haematol.2019.238154 Cite
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Type I Interferons Affect the Metabolic Fitness of CD8+ T Cells from Patients with Systemic Lupus Erythematosus

Scientists showed downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells.
[Nature Communications]
Buang, N., Tapeng, L., Gray, V., Sardini, A., Whilding, C., Lightstone, L., Cairns, T. D., Pickering, M. C., Behmoaras, J., Ling, G. S., & Botto, M. (2021). Type I interferons affect the metabolic fitness of CD8 + T cells from patients with systemic lupus erythematosus. Nature Communications, 12(1), 1980. https://doi.org/10.1038/s41467-021-22312-y Cite
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TAP Dysfunction in Dendritic Cells Enables Noncanonical Cross-Presentation for T Cell Priming

Scientists found that protective CD8+ T cells could be mobilized during viral infection even when TAP was absent in all hematopoietic cells.
[Nature Immunology]
Barbet, G., Nair-Gupta, P., Schotsaert, M., Yeung, S. T., Moretti, J., Seyffer, F., Metreveli, G., Gardner, T., Choi, A., Tortorella, D., Tampé, R., Khanna, K. M., García-Sastre, A., & Blander, J. M. (2021). TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming. Nature Immunology, 1–13. https://doi.org/10.1038/s41590-021-00903-7 Cite
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A Cross-Talk between CAR T Cell Subsets and the Tumor Microenvironment Is Essential for Sustained Cytotoxic Activity

Researchers report an essential cross-talk between CAR T cell subsets and the TME for tumor control in an immunocompetent mouse B cell lymphoma model of anti-CD19 CAR T cell therapy.
[Science Immunology]
Boulch, M., Cazaux, M., Loe-Mie, Y., Thibaut, R., Corre, B., Lemaître, F., Grandjean, C. L., Garcia, Z., & Bousso, P. (2021). A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity. Science Immunology, 6(57). https://doi.org/10.1126/sciimmunol.abd4344 Cite
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