Proteolysis-Targeting Chimera against BCL-XL Destroys Tumor-Infiltrating Regulatory T Cells

Scientists report their discovery of B-cell lymphoma extra-large as a potential molecular target of tumor-infiltrating Tregs.
[Nature Communications]
Kolb, R., De, U., Khan, S., Luo, Y., Kim, M.-C., Yu, H., Wu, C., Mo, J., Zhang, X., Zhang, P., Zhang, X., Borcherding, N., Koppel, D., Fu, Y.-X., Zheng, S. G., Avram, D., Zheng, G., Zhou, D., & Zhang, W. (2021). Proteolysis-targeting chimera against BCL-X L destroys tumor-infiltrating regulatory T cells. Nature Communications, 12(1), 1281. https://doi.org/10.1038/s41467-021-21573-x Cite
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Reduced Angiovasculogenic and Increased Inflammatory Profiles of Cord Blood Cells in Severe but Not Mild Preeclampsia

To better understand the effects of preeclampsia on angio-vasculogenesis and inflammatory networks in the fetus and to identify their biological signatures, researchers investigated the quantitative and functional characteristics of cord blood-derived mononuclear cells (MNCs) and CD31-positive MNCs.
[Scientific Reports]
Cho, S., Sohn, Y.-D., Kim, S., Rajakumar, A., Badell, M. L., Sidell, N., & Yoon, Y. (2021). Reduced angiovasculogenic and increased inflammatory profiles of cord blood cells in severe but not mild preeclampsia. Scientific Reports, 11(1), 3630. https://doi.org/10.1038/s41598-021-83146-8 Cite
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Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy

Researchers undertook experiments to define structural determinants of hypoxia-inducible factor that potentiate antitumor efficacy in cytotoxic T cells.
[Cancer Immunology Research]
Veliça, P., Cunha, P. P., Vojnovic, N., Foskolou, I. P., Bargiela, D., Gojkovic, M., Rundqvist, H., & Johnson, R. S. (2021). Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0561 Cite
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IRF4 Modulates the Response to BCR Activation in Chronic Lymphocytic Leukemia Regulating IKAROS and SYK

Scientists modulated IRF4 levels by transfecting chronic lymphocytic leukemia cells with an IRF4 vector or by silencing using small-interfering RNAs.
[Leukemia]
Maffei, R., Fiorcari, S., Benatti, S., Atene, C. G., Martinelli, S., Zucchini, P., Potenza, L., Luppi, M., & Marasca, R. (2021). IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK. Leukemia, 1–14. https://doi.org/10.1038/s41375-021-01178-5 Cite
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CD20 as a Gatekeeper of the Resting State of Human B Cells

Researchers demonstrated that CD20 controlled the nanoscale organization of receptors on the surface of resting B lymphocytes.
[Proceedings of the National Academy of Sciences of the United States of America]
Kläsener, K., Jellusova, J., Andrieux, G., Salzer, U., Böhler, C., Steiner, S. N., Albinus, J. B., Cavallari, M., Süß, B., Voll, R. E., Boerries, M., Wollscheid, B., & Reth, M. (2021). CD20 as a gatekeeper of the resting state of human B cells. Proceedings of the National Academy of Sciences, 118(7). https://doi.org/10.1073/pnas.2021342118 Cite
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Targeting Tumor-Associated Macrophages to Synergize Tumor Immunotherapy

Scientists summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition, tumor vaccines and adoptive cell transfer therapies.
[Signal Transduction and Targeted Therapy]
Xiang, X., Wang, J., Lu, D., & Xu, X. (2021). Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduction and Targeted Therapy, 6(1), 1–12. https://doi.org/10.1038/s41392-021-00484-9 Cite
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Therapeutic Solutions International Uses StemVacs™ Platform to Generate Personalized Adoptive T Cell Therapy Targeting Cancer Stem Cells

Therapeutic Solutions International, Inc., reported novel data and filing of a patent application demonstrating that StemVacs™ cells carrying proprietary sequences from the cancer-specific antigen Brother of the Regulator of Imprinted Sites, were able to elicit the generation of T cells capable of selectively killing cancer stem cells.
[Therapeutic Solutions International, Inc. (PR Newswire)]
Press Release
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DNA Hypomethylating Agents Increase Activation and Cytolytic Activity of CD8+ T Cells

Ex vivo, hypomethylating agents enhanced primary human CD8+ T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity.
[Molecular Cell]
Yau, H. L., Bell, E., Ettayebi, I., Almeida, F. C. de, Boukhaled, G. M., Shen, S. Y., Allard, D., Morancho, B., Marhon, S. A., Ishak, C. A., Gonzaga, I. M., Medina, T. da S., Singhania, R., Chakravarthy, A., Chen, R., Mehdipour, P., Pommey, S., Klein, C., Amarante-Mendes, G. P., … Carvalho, D. D. D. (2021). DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T cells. Molecular Cell, 0(0). https://doi.org/10.1016/j.molcel.2021.01.038 Cite
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The Innate Sensor ZBP1-IRF3 Axis Regulates Cell Proliferation in Multiple Myeloma

Investigators showed that Z-DNA-binding protein 1 (ZBP1) was selectively expressed in late B cell development in both human and mouse cells and it is required for optimal T-cell-dependent humoral immune responses.
[Haematologica]
Ponnusamy, K., Tzioni, M. M., Begum, M., Robinson, M. E., Caputo, V. S., Katsarou, A., Trasanidis, N., Xiao, X., Kostopoulos, I. V., Iskander, D., Roberts, I., Trivedi, P., Auner, H. W., Naresh, K., Chaidos, A., & Karadimitris, A. (2020). The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma. Haematologica. https://doi.org/10.3324/haematol.2020.274480 Cite
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Epitope Spreading toward Wild-Type Melanocyte-Lineage Antigens Rescues Suboptimal Immune Checkpoint Blockade Responses

Scientists report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes.
[Science Translational Medicine]
Lo, J. A., Kawakubo, M., Juneja, V. R., Su, M. Y., Erlich, T. H., LaFleur, M. W., Kemeny, L. V., Rashid, M., Malehmir, M., Rabi, S. A., Raghavan, R., Allouche, J., Kasumova, G., Frederick, D. T., Pauken, K. E., Weng, Q. Y., Silva, M. P. da, Xu, Y., Sande, A. A. J. van der, … Fisher, D. E. (2021). Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses. Science Translational Medicine, 13(581). https://doi.org/10.1126/scitranslmed.abd8636 Cite
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Common Clonal Origin of Conventional T Cells and Induced Regulatory T Cells in Breast Cancer Patients

Scientists analyzed Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing.
[Nature Communications]
Xydia, M., Rahbari, R., Ruggiero, E., Macaulay, I., Tarabichi, M., Lohmayer, R., Wilkening, S., Michels, T., Brown, D., Vanuytven, S., Mastitskaya, S., Laidlaw, S., Grabe, N., Pritsch, M., Fronza, R., Hexel, K., Schmitt, S., Müller-Steinhardt, M., Halama, N., … Beckhove, P. (2021). Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients. Nature Communications, 12(1), 1119. https://doi.org/10.1038/s41467-021-21297-y Cite
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