Fine-Mapping, Trans-Ancestral and Genomic Analyses Identify Causal Variants, Cells, Genes and Drug Targets for Type 1 Diabetes

Researchers reported the largest and most diverse genetic study of type 1 diabetes to date, yielding 78 genome-wide-significant regions, including 36 that are new.
[Nature Genetics]
Robertson, C. C., Inshaw, J. R. J., Onengut-Gumuscu, S., Chen, W.-M., Santa Cruz, D. F., Yang, H., Cutler, A. J., Crouch, D. J. M., Farber, E., Bridges, S. L., Edberg, J. C., Kimberly, R. P., Buckner, J. H., Deloukas, P., Divers, J., Dabelea, D., Lawrence, J. M., Marcovina, S., Shah, A. S., … Rich, S. S. (2021). Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nature Genetics, 1–10. https://doi.org/10.1038/s41588-021-00880-5 Cite
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TP53 Missense Mutations in PDAC Are Associated with Enhanced Fibrosis and an Immunosuppressive Microenvironment

Researchers suggested that missense p53 mutations might contribute to worse pancreatic ductal adenocarcinoma prognosis by promoting a more vigorous fibrotic tumor microenvironment and impeding the ability of the immune system to eliminate the cancer cells.
[Proceedings of the National Academy of Sciences of the United States of America]
Maddalena, M., Mallel, G., Nataraj, N. B., Shreberk-Shaked, M., Hassin, O., Mukherjee, S., Arandkar, S., Rotkopf, R., Kapsack, A., Lambiase, G., Pellegrino, B., Ben-Isaac, E., Golani, O., Addadi, Y., Hajaj, E., Eilam, R., Straussman, R., Yarden, Y., Lotem, M., & Oren, M. (2021). TP53 missense mutations in PDAC are associated with enhanced fibrosis and an immunosuppressive microenvironment. Proceedings of the National Academy of Sciences, 118(23). https://doi.org/10.1073/pnas.2025631118 Cite
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CF33-hNIS-antiPDL1 Virus Primes Pancreatic Ductal Adenocarcinoma for Enhanced Anti-PD-L1 Therapy

Oncolytic viral chimera, CF33-hNIS-antiPDL1 genetically modified to express anti-human PD-L1 antibody and CF33-hNIS-Δ without the anti-PD-L1 gene, were used to investigate the immunogenic effects of oncolytic virus and virus-delivered anti-PD-L1 in pancreatic ductal adenocarcinoma in vitro.
[Cancer Gene Therapy]
Zhang, Z., Yang, A., Chaurasiya, S., Park, A. K., Lu, J., Kim, S.-I., Warner, S. G., Yuan, Y.-C., Liu, Z., Han, H., Von Hoff, D., Fong, Y., & Woo, Y. (2021). CF33-hNIS-antiPDL1 virus primes pancreatic ductal adenocarcinoma for enhanced anti-PD-L1 therapy. Cancer Gene Therapy, 1–12. https://doi.org/10.1038/s41417-021-00350-4 Cite
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PRC2 Loss of Function Confers a Targetable Vulnerability to BET Proteins in T-ALL

The authors analyzed Polycomb Repressor Complex 2 (PRC2) alterations in a large series of 218 adult T-cell acute lymphoblastic leukemia (T-ALL) patients and found that PRC2 genetic lesions were frequent events in T-ALL and were not restricted to ETP-ALL.
[Blood]
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60 Years Young: The Evolving Role of Allogeneic Hematopoietic Stem Cell Transplantation in Cancer Immunotherapy

The authors review the historical basis underpinning the development of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as advances in knowledge obtained by defining mechanisms of allo-HSCT activity.
[Cancer Research]
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Bristol Myers Squibb Announces Positive Topline Results from Phase III TRANSFORM Trial Evaluating Breyanzi (lisocabtagene maraleucel) Versus Chemotherapy Followed by Stem Cell Transplant in Second-Line Relapsed or Refractory Large B-cell Lymphoma

Bristol Myers Squibb announced positive results from TRANSFORM, a Phase III study evaluating Breyanzi as a second-line treatment in adults with relapsed or refractory large B-cell lymphoma compared to salvage therapy followed by high-dose chemotherapy and hematopoietic stem cell transplant.
[Bristol Myers Squibb]
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B2M Gene Expression Shapes the Immune Landscape of Lung Adenocarcinoma and Determines the Response to Immunotherapy

Scientists performed an integrative analysis of the mutational and transcriptional profiles of large cohorts of non-small-cell lung cancer patients and found that epigenetic downregulation of B2M was common.
[Immunology]
Zhao, Y., Cao, Y., Chen, Y., Wu, L., Hang, H., Jiang, C., & Zhou, X. (n.d.). B2M gene expression shapes the immune landscape of lung adenocarcinoma and determines the response to immunotherapy. Immunology, n/a(n/a). https://doi.org/10.1111/imm.13384 Cite
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Blocking Siglec-10hi Tumor-Associated Macrophages Improves Anti-Tumor Immunity and Enhances Immunotherapy for Hepatocellular Carcinoma

Immunohistochemistry and flow cytometry were performed to detect the characteristics of sialic acid-binding immunoglobulin-like lectin 10high (Siglec-10hi) tumor-associated macrophages and explore their impact on the tumor microenvironment of hepatocellular carcinoma.
[Experimental Hematology & Oncology]
Xiao, N., Zhu, X., Li, K., Chen, Y., Liu, X., Xu, B., Lei, M., Xu, J., & Sun, H.-C. (2021). Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma. Experimental Hematology & Oncology, 10(1), 36. https://doi.org/10.1186/s40164-021-00230-5 Cite
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Imaging CAR T-Cell Kinetics in Solid Tumors: Translational Implications

Scientists conducted dual tumor and T-cell imaging by use of a bioluminescent reporter and positron emission tomography in clinically relevant mouse models of pleural mesothelioma and non-small cell lung cancer.
[Molecular Therapy-Oncolytics]
Skovgard, M. S., Hocine, H. R., Saini, J. K., Moroz, M., Bellis, R. Y., Banerjee, S., Morello, A., Ponomarev, V., Villena-Vargas, J., & Adusumilli, P. S. (2021). Imaging CAR T-Cell Kinetics in Solid Tumors: Translational Implications. Molecular Therapy - Oncolytics, 0(0). https://doi.org/10.1016/j.omto.2021.06.006 Cite
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Immune Modulation via Adipose Derived Mesenchymal Stem Cells Is Driven by Donor Sex In Vitro

The authors examined the potency and functionality of both female and male adipose derived mesenchymal stem cells in order to gain further insights into donor selection.
[Scientific Reports]
Mckinnirey, F., Herbert, B., Vesey, G., & McCracken, S. (2021). Immune modulation via adipose derived Mesenchymal Stem cells is driven by donor sex in vitro. Scientific Reports, 11(1), 12454. https://doi.org/10.1038/s41598-021-91870-4 Cite
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Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products

Scientists discuss the progress made in induced pluripotent stem cells (iPSC)-derived T cells and provides a roadmap for the development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.
[Pharmaceutical Research]
Sadeqi Nezhad, M., Abdollahpour-Alitappeh, M., Rezaei, B., Yazdanifar, M., & Seifalian, A. M. (2021). Induced Pluripotent Stem Cells (iPSCs) Provide a Potentially Unlimited T Cell Source for CAR-T Cell Development and Off-the-Shelf Products. Pharmaceutical Research. https://doi.org/10.1007/s11095-021-03067-z Cite
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