Targeted Delivery of CRISPR-Cas9 and Transgenes Enables Complex Immune Cell Engineering

The authors developed a one-step strategy using engineered lentiviral particles to introduce Cas9 RNPs and a CAR transgene into primary human T cells without electroporation.
[Cell Reports]
Hamilton, J. R., Tsuchida, C. A., Nguyen, D. N., Shy, B. R., McGarrigle, E. R., Espinoza, C. R. S., Carr, D., Blaeschke, F., Marson, A., & Doudna, J. A. (2021). Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering. Cell Reports, 35(9). https://doi.org/10.1016/j.celrep.2021.109207 Cite
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Pro-Resolving Lipid Mediator Lipoxin A4 Attenuates Neuro-Inflammation by Modulating T Cell Responses and Modifies the Spinal Cord Lipidome

Scientists provided in vivo evidence that treatment with the SPM lipoxin A4 ameliorates clinical symptoms of experimental autoimmune encephalomyelitis and inhibited CD4+ and CD8+ T cell infiltration into the central nervous system.
[Cell Reports]
Troletti, C. D., Enzmann, G., Chiurchiù, V., Kamermans, A., Tietz, S. M., Norris, P. C., Jahromi, N. H., Leuti, A., Pol, S. M. A. van der, Schouten, M., Serhan, C. N., Vries, H. E. de, Engelhardt, B., & Kooij, G. (2021). Pro-resolving lipid mediator lipoxin A4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome. Cell Reports, 35(9). https://doi.org/10.1016/j.celrep.2021.109201 Cite
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An Oncolytic Virus Expressing IL-15/IL-15Rα Combined with off-the-Shelf EGFR-CAR NK Cells Targets Glioblastoma

Scientists generated a herpes simplex 1-based oncolytic viruses expressing human IL-15/IL-15Rα sushi domain fusion protein, as well as off-the-shelf EGFR-CAR NK cells, and studied their monotherapy and combination efficacy in vitro and in multiple glioblastoma mouse models.
[Cancer Research]
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DLL1 Orchestrates CD8+ T Cells to Induce Long-term Vascular Normalization and Tumor Regression

Scientists showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung tumor microenvironment induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ–expressing CD8+ T cells and the polarization of M1-like macrophages.
[Proceedings of the National Academy of Sciences of the United States of America]
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A Novel Mouse Model for Liver Metastasis of Prostate Cancer Reveals Dynamic Tumour-Immune Cell Communication

The authors developed a rapid and immune sufficient mouse model for liver metastasis of prostate cancer via orthotopic injection of organoids from PbCre+; rb1f/f;p53f/f mice.
[Cell Proliferation]
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Modulation of the Immune Microenvironment of High-Risk Ductal Carcinoma In Situ by Intralesional Pembrolizumab Injection

Patients with high-risk DCIS were enrolled in this 3×3 Phase I dose-escalation pilot study of two, four and eight mg intralesional injections of the PD-1 immune checkpoint inhibitor, pembrolizumab.
[npj Breast Cancer]
Glencer, A. C., Wong, J. M., Hylton, N. M., Krings, G., McCune, E., Rothschild, H. T., Loveday, T. A., Alvarado, M. D., Esserman, L. J., & Campbell, M. J. (2021). Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection. Npj Breast Cancer, 7(1), 1–10. https://doi.org/10.1038/s41523-021-00267-z Cite
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SARS-CoV-2 Human T Cell Epitopes: Adaptive Immune Response against COVID-19

Investigators review how epitopes identified throughout the SARS-CoV-2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance.
[Cell Host & Microbe]
Grifoni, A., Sidney, J., Vita, R., Peters, B., Crotty, S., Weiskopf, D., & Sette, A. (2021). SARS-CoV-2 Human T cell Epitopes: adaptive immune response against COVID-19. Cell Host & Microbe, 0(0). https://doi.org/10.1016/j.chom.2021.05.010 Cite
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Immunobiology and Pathogenesis of Hepatitis B Virus Infection

The authors review our current knowledge on the immunobiology and pathogenesis of Hepatitis B virus infection, focusing in particular on the role of CD8+ T cells and on several recent breakthroughs that challenge current dogmas.
[Nature Reviews Immunology]
Iannacone, M., & Guidotti, L. G. (2021). Immunobiology and pathogenesis of hepatitis B virus infection. Nature Reviews Immunology, 1–14. https://doi.org/10.1038/s41577-021-00549-4 Cite
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cIAP1/2 Antagonism Eliminates MHC Class I–Negative Tumors through T Cell–Dependent Reprogramming of Mononuclear Phagocytes

The authors showed that induction of noncanonical NF-κB signaling induces T cell–dependent immune responses, even in β2-microglobulin–deficient tumors, demonstrating that direct CD8 T cell recognition of tumor cell–expressed MHC class I was not required.
[Science Translational Medicine]
Roehle, K., Qiang, L., Ventre, K. S., Heid, D., Ali, L. R., Lenehan, P., Heckler, M., Crowley, S. J., Stump, C. T., Ro, G., Godicelj, A., Bhuiyan, A. M., Yang, A., Rey, M. Q. del, Biary, T., Luoma, A. M., Bruck, P. T., Tegethoff, J. F., Nopper, S. L., … Dougan, S. K. (2021). cIAP1/2 antagonism eliminates MHC class I–negative tumors through T cell–dependent reprogramming of mononuclear phagocytes. Science Translational Medicine, 13(594). https://doi.org/10.1126/scitranslmed.abf5058 Cite
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Preexisting and Post-COVID-19 Immune Responses to SARS-CoV-2 in Cancer Patients

Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers.
[Cancer Discovery]
Bilich, T., Roerden, M., Maringer, Y., Nelde, A., Heitmann, J. S., Dubbelaar, M. L., Peter, A., Horber, S., Bauer, J., Rieth, J., Wacker, M., Berner, F., Flatz, L., Held, S., Brossart, P., Marklin, M., Wagner, P., Erne, E., Klein, R., … Walz, J. S. (2021). Preexisting and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-21-0191 Cite
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The Multiple Myeloma Microenvironment Is Defined by an Inflammatory Stromal Cell Landscape

Investigators generated paired single-cell transcriptomic datasets of tumor cells and the bone marrow immune and stromal microenvironment in multiple myeloma.
[Nature Immunology]
de Jong, M. M. E., Kellermayer, Z., Papazian, N., Tahri, S., Hofste op Bruinink, D., Hoogenboezem, R., Sanders, M. A., van de Woestijne, P. C., Bos, P. K., Khandanpour, C., Vermeulen, J., Moreau, P., van Duin, M., Broijl, A., Sonneveld, P., & Cupedo, T. (2021). The multiple myeloma microenvironment is defined by an inflammatory stromal cell landscape. Nature Immunology, 1–12. https://doi.org/10.1038/s41590-021-00931-3 Cite
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