Epigenetic Scars of CD8+ T Cell Exhaustion Persist after Cure of Chronic Infection in Humans

Researchers showed that the epigenetic state of exhaustion was largely irreversible, even after curative therapy. Analysis of chromatin accessibility in HCV- and HIV-specific responses identified a core epigenetic program of exhaustion in CD8+ T cells, which underwent only limited remodeling before and after resolution of infection.
[Nature Immunology]
Yates, K. B., Tonnerre, P., Martin, G. E., Gerdemann, U., Al Abosy, R., Comstock, D. E., Weiss, S. A., Wolski, D., Tully, D. C., Chung, R. T., Allen, T. M., Kim, A. Y., Fidler, S., Fox, J., Frater, J., Lauer, G. M., Haining, W. N., & Sen, D. R. (2021). Epigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans. Nature Immunology, 22(8), 1020–1029. https://doi.org/10.1038/s41590-021-00979-1 Cite
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Dendritic Cell Migration in Inflammation and Immunity

Investigators discuss the migratory routes and immunological consequences of distinct dendritic cell (DC) subsets, the molecular basis and regulatory mechanisms of migratory signaling in DCs, and the association of DC migration with the pathogenesis of autoimmune and infectious diseases.
[Cellular & Molecular Immunology]
Liu, J., Zhang, X., Cheng, Y., & Cao, X. (2021). Dendritic cell migration in inflammation and immunity. Cellular & Molecular Immunology, 1–11. https://doi.org/10.1038/s41423-021-00726-4 Cite
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An Epigenetic GPI Anchor Defect Impairs TLR4 Signaling in the B Cell Transdifferentiation Model for Primary Human Monocytes BLaER1

The authors identified an important caveat when investigating TLR4-driven signaling in BLaER1 cells. They showed that this model contained glycosylphosphatidylinositol anchor-deficient cells, which lacked CD14 surface expression when differentiated to monocytes, resulting in diminished LPS/TLR4 but not TLR7/TLR8 responsiveness.
[Scientific Reports]
Wegner, J., Zillinger, T., Schlee-Guimaraes, T., Bartok, E., & Schlee, M. (2021). An epigenetic GPI anchor defect impairs TLR4 signaling in the B cell transdifferentiation model for primary human monocytes BLaER1. Scientific Reports, 11(1), 14983. https://doi.org/10.1038/s41598-021-94386-z Cite
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Increase in Polymorphonuclear Myeloid-Derived Suppressor Cells and Regulatory T-Cells in Children with B-Cell Acute Lymphoblastic Leukemia

Scientists observed a reduction in the levels of CD4+ T cells and an increase in both the polymorphonuclear MDSCs and Tregs.
[Scientific Reports]
Zahran, A. M., Shibl, A., Rayan, A., Mohamed, M. A. E. H., Osman, A. M. M., Saad, K., Mahmoud, K. H., Ghandour, A. M. A., Elsayh, K. I., & El-Badawy, O. (2021). Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia. Scientific Reports, 11(1), 15039. https://doi.org/10.1038/s41598-021-94469-x Cite
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A Human CD137×PD-L1 Bispecific Antibody Promotes Anti-tumor Immunity via Context-Dependent T Cell Costimulation and Checkpoint Blockade

Researchers described a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations.
[Nature Communications]
Geuijen, C., Tacken, P., Wang, L.-C., Klooster, R., van Loo, P. F., Zhou, J., Mondal, A., Liu, Y., Kramer, A., Condamine, T., Volgina, A., Hendriks, L. J. A., van der Maaden, H., Rovers, E., Engels, S., Fransen, F., den Blanken-Smit, R., Zondag-van der Zande, V., Basmeleh, A., … Throsby, M. (2021). A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade. Nature Communications, 12(1), 4445. https://doi.org/10.1038/s41467-021-24767-5 Cite
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DCision-Making in Tumors Governs T Cell Anti-Tumor Immunity

The authors summarize how T cell activation is controlled by dendritic cells and how the tumor microenvironment alters dendritic cell properties in the context of the anti-tumor immune cycle.
[Oncogene]
Alfei, F., Ho, P.-C., & Lo, W.-L. (2021). DCision-making in tumors governs T cell anti-tumor immunity. Oncogene, 1–9. https://doi.org/10.1038/s41388-021-01946-8 Cite
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Phenotype, Specificity and Avidity of Antitumour CD8+ T Cells in Melanoma

Scientists showed, by linking the antigenic specificity of TCRs and the cellular phenotype of melanoma-infiltrating lymphocytes at single-cell resolution, that tumor specificity shaped the expression state of intratumoural CD8+ T cells.
[Nature]
Oliveira, G., Stromhaug, K., Klaeger, S., Kula, T., Frederick, D. T., Le, P. M., Forman, J., Huang, T., Li, S., Zhang, W., Xu, Q., Cieri, N., Clauser, K. R., Shukla, S. A., Neuberg, D., Justesen, S., MacBeath, G., Carr, S. A., Fritsch, E. F., … Wu, C. J. (2021). Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature, 1–7. https://doi.org/10.1038/s41586-021-03704-y Cite
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A Multilayered Immune System through the Lens of Unconventional T Cells

Scientists recast unconventional T cell subsets according to the class of ligand that they recognize; their expression of semi-invariant or diverse T cell receptors; the structural features that underlie ligand recognition; their acquisition of effector functions in the thymus or periphery; and their distinct functional properties.
[Nature]
Mayassi, T., Barreiro, L. B., Rossjohn, J., & Jabri, B. (2021). A multilayered immune system through the lens of unconventional T cells. Nature, 595(7868), 501–510. https://doi.org/10.1038/s41586-021-03578-0 Cite
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BATF and IRF4 Cooperate to Counter Exhaustion in Tumor-Infiltrating CAR T Cells

Overexpression of BATF in CD8+ T cells expressing a chimeric antigen receptor (CAR) promoted the survival and expansion of tumor-infiltrating CAR T cells, increased the production of effector cytokines, and decreased the expression of inhibitory receptors.
[Nature Immunology]
Seo, H., González-Avalos, E., Zhang, W., Ramchandani, P., Yang, C., Lio, C.-W. J., Rao, A., & Hogan, P. G. (2021). BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells. Nature Immunology, 1–13. https://doi.org/10.1038/s41590-021-00964-8 Cite
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Alternative Pathways for the Development of Lymphoid Structures in Humans

In humans, JAK3 and γc deficiencies resulted in severe combined immunodeficiency characterized by an absence of T cells, natural killer cells, innate lymphoid cells, and presumably lymphoid tissue inducer cells.
[Proceedings of the National Academy of Sciences of the United States of America]
Berteloot, L., Molina, T. J., Bruneau, J., Picard, C., Barlogis, V., Secq, V., Abdo, C., Boddaert, N., Griscelli, C., Neven, B., & Fischer, A. (2021). Alternative pathways for the development of lymphoid structures in humans. Proceedings of the National Academy of Sciences, 118(29). https://doi.org/10.1073/pnas.2108082118 Cite
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Non-Terminally Exhausted Tumor-Resident Memory HBV-Specific T Cell Responses Correlate with Relapse-Free Survival in Hepatocellular Carcinoma

Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, researchers detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens.
[Immunity]
Cheng, Y., Gunasegaran, B., Singh, H. D., Dutertre, C.-A., Loh, C. Y., Lim, J. Q., Crawford, J. C., Lee, H. K., Zhang, X., Lee, B., Becht, E., Lim, W. J., Yeong, J., Chan, C. Y., Chung, A., Goh, B. K. P., Chow, P. K. H., Chan, J. K. Y., Ginhoux, F., … Newell, E. W. (2021). Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.06.013 Cite
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