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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High-Throughput and Single-Cell T Cell Receptor Sequencing Technologies

The authors highlight advances in high-throughput sequencing technologies to identify TCR sequences and describe how they have been applied to discover fundamental insights into T cell-mediated immunity.
[Nature Methods]
Pai, J. A., & Satpathy, A. T. (2021). High-throughput and single-cell T cell receptor sequencing technologies. Nature Methods, 1–12. https://doi.org/10.1038/s41592-021-01201-8 Cite
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Depletion of High-Content CD14+ Cells from Apheresis Products Is Critical for the Successful Transduction and Expansion of CAR T Cells during Large-Scale cGMP Manufacturing

Investigators found that high CD14+ cell content posed a challenge for manufacturing CAR T cells especially in patients with non-Hodgkin’s lymphoma and multiple myeloma due to the non-specific phagocytosis of the magnetic beads used to activate CD3+ T cells.
[Molecular Therapy-Methods & Clinical Development]
Wang, X., Borquez-Ojeda, O., Stefanski, J., Du, F., Qu, J., Chaudhari, J., Thummar, K., Zhu, M., Shen, L., Hall, M., Gautam, P., Wang, Y., Senechal, B., Sikder, D., Adusumilli, P. S., Brentjens, R. J., Curran, K., Geyer, M. B., Mailankhody, S., … Rivière, I. (2021). Depletion of High-Content CD14+ Cells from Apheresis Products is Critical for the Successful Transduction and Expansion of CAR T cells during Large-scale cGMP Manufacturing. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2021.06.014 Cite
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Characterization of Neoantigen-Specific T Cells in Cancer Resistant to Immune Checkpoint Therapies

Leveraging the use of mass cytometry combined with multiplex major histocompatibility complex class I tetramer staining, researchers screened and identified tumor neoantigen–specific CD8+ T cells in the Lewis Lung carcinoma tumor model.
[Proceedings of the National Academy of Sciences of the United States of America]
Wang, X., Borquez-Ojeda, O., Stefanski, J., Du, F., Qu, J., Chaudhari, J., Thummar, K., Zhu, M., Shen, L., Hall, M., Gautam, P., Wang, Y., Senechal, B., Sikder, D., Adusumilli, P. S., Brentjens, R. J., Curran, K., Geyer, M. B., Mailankhody, S., … Rivière, I. (2021). Depletion of High-Content CD14+ Cells from Apheresis Products is Critical for the Successful Transduction and Expansion of CAR T cells during Large-scale cGMP Manufacturing. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2021.06.014 Cite
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Cell-Autonomous Inflammation of BRCA1-Deficient Ovarian Cancers Drives Both Tumor-Intrinsic Immunoreactivity and Immune Resistance via STING

Genetic deletion or methylation of DNA-sensing/IFN genes or CCL5 chemokine was identified as a potential mechanism to attenuate T cell inflammation.
[Cell Reports]
Bruand, M., Barras, D., Mina, M., Ghisoni, E., Morotti, M., Lanitis, E., Fahr, N., Desbuisson, M., Grimm, A., Zhang, H., Chong, C., Dagher, J., Chee, S., Tsianou, T., Dorier, J., Stevenson, B. J., Iseli, C., Ronet, C., Bobisse, S., … Coukos, G. (2021). Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING. Cell Reports, 36(3). https://doi.org/10.1016/j.celrep.2021.109412 Cite
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SPNS2 Enables T Cell Egress from Lymph Nodes during an Immune Response

Using a model of dermal inflammation, investigators demonstrated that SPNS2 supplies the S1P that guided T cells out of lymph nodes with an ongoing immune response.
[Cell Reports]
Okuniewska, M., Fang, V., Baeyens, A., Raghavan, V., Lee, J.-Y., Littman, D. R., & Schwab, S. R. (2021). SPNS2 enables T cell egress from lymph nodes during an immune response. Cell Reports, 36(2). https://doi.org/10.1016/j.celrep.2021.109368 Cite
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Systemic Inhibition of PTPN22 Augments Anticancer Immunity

In mice, lack of PTPN22 augmented antitumor activity with greater infiltration and activation of macrophages, natural killer (NK) cells, and T cells.
[Journal of Clinical Investigation]
Ho, W. J., Croessmann, S., Lin, J., Phyo, Z. H., Charmsaz, S., Danilova, L., Mohan, A. A., Gross, N. E., Chen, F., Dong, J., Aggarwal, D., Bai, Y., Wang, J., He, J., Leatherman, J. M., Yarchoan, M., Armstrong, T. D., Zaidi, N., Fertig, E. J., … Jaffee, E. M. (2021). Systemic inhibition of PTPN22 augments anticancer immunity. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI146950 Cite
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Constrained TCRγδ-Associated Syk Activity Engages PI3K to Facilitate Thymic Development of IL-17A–Secreting γδ T Cells

Increasing or decreasing Syk activity by stimulating the γδ T cell receptor (TCRγδ) or inhibiting Syk, respectively, substantially reduced γδ17 cell numbers.
[Science Signaling]
Sumaria, N., Martin, S., & Pennington, D. J. (2021). Constrained TCRγδ-associated Syk activity engages PI3K to facilitate thymic development of IL-17A–secreting γδ T cells. Science Signaling, 14(692). https://doi.org/10.1126/scisignal.abc5884 Cite
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Transcriptional Programs of Neoantigen-Specific TIL in Anti-PD-1-Treated Lung Cancers

Scientists identified mutation-associated neoantigens (MANA)-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers.
[Nature]
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Castration-Mediated IL-8 Promotes Myeloid Infiltration and Prostate Cancer Progression

Scientists established a novel mechanism by which castration mediated IL-8 secretion and subsequent polymorphonuclear myeloid-derived suppressor cells infiltration.
[Nature Cancer]
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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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