In Vivo CRISPR Screening Reveals Nutrient Signaling Processes Underpinning CD8+ T Cell Fate Decisions

Scientists established that nutrient uptake and signaling are key determinants of T cell fate and shape the quantity and quality of memory T cell responses.
[Cell]
Huang, H., Zhou, P., Wei, J., Long, L., Shi, H., Dhungana, Y., Chapman, N. M., Fu, G., Saravia, J., Raynor, J. L., Liu, S., Palacios, G., Wang, Y.-D., Qian, C., Yu, J., & Chi, H. (2021). In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions. Cell, 0(0). https://doi.org/10.1016/j.cell.2021.02.021 Cite
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METTL3-Dependent m6A Modification Programs T Follicular Helper Cell Differentiation

Researchers showed conditional deletion of METTL3 in CD4+ T cells impaired TFH differentiation and germinal center responses in a cell-intrinsic manner in mice.
[Nature Communications]
Yao, Y., Yang, Y., Guo, W., Xu, L., You, M., Zhang, Y.-C., Sun, Z., Cui, X., Yu, G., Qi, Z., Liu, J., Wang, F., Liu, J., Zhao, T., Ye, L., Yang, Y.-G., & Yu, S. (2021). METTL3-dependent m 6 A modification programs T follicular helper cell differentiation. Nature Communications, 12(1), 1333. https://doi.org/10.1038/s41467-021-21594-6 Cite
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Pre-Mitotic Genome Re-Organisation Bookends the B Cell Differentiation Process

Scientists elucidated the chromosome conformational changes in B lymphocytes as they differentiated and expanded from a naive, quiescent state into antibody secreting plasma cells.
[Nature Communications]
Chan, W. F., Coughlan, H. D., Zhou, J. H. S., Keenan, C. R., Bediaga, N. G., Hodgkin, P. D., Smyth, G. K., Johanson, T. M., & Allan, R. S. (2021). Pre-mitotic genome re-organisation bookends the B cell differentiation process. Nature Communications, 12(1), 1344. https://doi.org/10.1038/s41467-021-21536-2 Cite
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Multimodal Pooled Perturb-Cite-Seq Screens in Patient Models Define Mechanisms of Cancer Immune Evasion

In patient-derived melanoma cells and autologous tumor-infiltrating lymphocyte co-cultures, scientists profiled transcriptomes and 20 proteins in ~218,000 cells under ~750 perturbations associated with cancer cell-intrinsic immune checkpoint inhibitor resistance
[Nature Genetics]
Frangieh, C. J., Melms, J. C., Thakore, P. I., Geiger-Schuller, K. R., Ho, P., Luoma, A. M., Cleary, B., Jerby-Arnon, L., Malu, S., Cuoco, M. S., Zhao, M., Ager, C. R., Rogava, M., Hovey, L., Rotem, A., Bernatchez, C., Wucherpfennig, K. W., Johnson, B. E., Rozenblatt-Rosen, O., … Izar, B. (2021). Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion. Nature Genetics, 1–10. https://doi.org/10.1038/s41588-021-00779-1 Cite
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Affinity-Matured Hla Class II Dimers for Robust Staining of Antigen-Specific CD4+ T Cells

Researchers produced affinity-matured class II dimers that stain antigen-specific T cells better than conventional multimers in both in vitro and ex vivo analyses.
[Nature Biotechnology]
Sugata, K., Matsunaga, Y., Yamashita, Y., Nakatsugawa, M., Guo, T., Halabelian, L., Ohashi, Y., Saso, K., Rahman, M. A., Anczurowski, M., Wang, C.-H., Murata, K., Saijo, H., Kagoya, Y., Ly, D., Burt, B. D., Butler, M. O., Mak, T. W., & Hirano, N. (2021). Affinity-matured HLA class II dimers for robust staining of antigen-specific CD4 + T cells. Nature Biotechnology, 1–10. https://doi.org/10.1038/s41587-021-00836-4 Cite
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Effector and Stem-Like Memory Cell Fates Are Imprinted in Distinct Lymph Node Niches Directed by CXCR3 Ligands

Scientists developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate.
[Nature Immunology]
Duckworth, B. C., Lafouresse, F., Wimmer, V. C., Broomfield, B. J., Dalit, L., Alexandre, Y. O., Sheikh, A. A., Qin, R. Z., Alvarado, C., Mielke, L. A., Pellegrini, M., Mueller, S. N., Boudier, T., Rogers, K. L., & Groom, J. R. (2021). Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands. Nature Immunology, 1–15. https://doi.org/10.1038/s41590-021-00878-5 Cite
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Immunomodulating Nano-Adaptors Potentiate Antibody-Based Cancer Immunotherapy

Investigators built up a versatile antibody immobilization platform by conjugating anti-IgG antibody onto the nanoparticle surface.
[Nature Communications]
Jiang, C.-T., Chen, K.-G., Liu, A., Huang, H., Fan, Y.-N., Zhao, D.-K., Ye, Q.-N., Zhang, H.-B., Xu, C.-F., Shen, S., Xiong, M.-H., Du, J.-Z., Yang, X.-Z., & Wang, J. (2021). Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy. Nature Communications, 12(1), 1359. https://doi.org/10.1038/s41467-021-21497-6 Cite
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Deletion of the Mitochondria-Shaping Protein Opa1 during Early Thymocyte Maturation Impacts Mature Memory T Cell Metabolism

Investigators showed that optic atrophy 1 was necessary for thymocyte maturation at the double negative 3 stage when rearrangement of the T cell receptor β locus occurred.
[Cell Death & Differentiation]
Corrado, M., Samardžić, D., Giacomello, M., Rana, N., Pearce, E. L., & Scorrano, L. (2021). Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism. Cell Death & Differentiation, 1–13. https://doi.org/10.1038/s41418-021-00747-6 Cite
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Isoginkgetin Derivative IP2 Enhances the Adaptive Immune Response against Tumor Antigens

Scientists showed that IP2 increased pioneer translation product-derived antigen presentation in cancer cells in vitro and impaired tumor growth in vivo.
[Communications Biology]
Darrigrand, R., Pierson, A., Rouillon, M., Renko, D., Boulpicante, M., Bouyssié, D., Mouton-Barbosa, E., Marcoux, J., Garcia, C., Ghosh, M., Alami, M., & Apcher, S. (2021). Isoginkgetin derivative IP2 enhances the adaptive immune response against tumor antigens. Communications Biology, 4(1), 1–14. https://doi.org/10.1038/s42003-021-01801-2 Cite
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Inhibition of Phospholipases Suppresses Progression of Psoriasis through Modulation of Inflammation

Investigators transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B.
[Experimental Biology and Medicine]
Gao, Y., Lu, J., Bao, X., Yi, X., Peng, C., Chen, W., Zhen, T., Shi, Y., Xing, K., Zhu, S., & Ding, Y. (2021). Inhibition of phospholipases suppresses progression of psoriasis through modulation of inflammation. Experimental Biology and Medicine, 1535370221993424. https://doi.org/10.1177/1535370221993424 Cite
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Siglec-6 Is a Target for Chimeric Antigen Receptor T-cell Treatment of Chronic Lymphocytic Leukemia

Researchers evaluated CAR-T cells specific for Siglec-6, an antigen expressed in chronic lymphocytic leukemia (CLL), as a novel CAR-T cell treatment for CLL.
[Leukemia]
Kovalovsky, D., Yoon, J. H., Cyr, M. G., Simon, S., Voynova, E., Rader, C., Wiestner, A., Alejo, J., Pittaluga, S., & Gress, R. E. (2021). Siglec-6 is a target for chimeric antigen receptor T-cell treatment of chronic lymphocytic leukemia. Leukemia, 1–11. https://doi.org/10.1038/s41375-021-01188-3 Cite
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