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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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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T-Regulatory Cells Predict Clinical Outcome in Soft Tissue Sarcoma Patients: A Clinico-Pathological Study

Investigators analyzed tumor-infiltrating lymphocytes and immune checkpoint molecules in soft tissue sarcomas, and assessed their prognostic impact regarding local recurrence, distant metastasis, and overall survival.
[British Journal of Cancer]
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TCF1 in T Cell Immunity: A Broadened Frontier

Scientists summarize the key findings on TCF1 across the fields of T cell immunity and reflect on the possibility of exploring TCF1 and its downstream transcriptional programmes as therapeutic targets for improving antiviral and antitumour immunity.
[Nature Reviews Immunology]
Zhao, X., Shan, Q., & Xue, H.-H. (2021). TCF1 in T cell immunity: a broadened frontier. Nature Reviews Immunology, 1–11. https://doi.org/10.1038/s41577-021-00563-6 Cite
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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T Cell Immunity

The authors showed that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after immune checkpoint blockade therapy.
[Cancer Cell]
Chow, A., Schad, S., Green, M. D., Hellmann, M. D., Allaj, V., Ceglia, N., Zago, G., Shah, N. S., Sharma, S. K., Mattar, M., Chan, J., Rizvi, H., Zhong, H., Liu, C., Bykov, Y., Zamarin, D., Shi, H., Budhu, S., Wohlhieter, C., … Merghoub, T. (2021). Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2021.05.006 Cite
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Lentiviral Vector Induces High-Quality Memory T Cells via Dendritic Cells Transduction

With a mycobacterial immunogen, scientists observed distinct functional signatures and memory phenotype in lentiviral vector- or Adenovirus type 5-immunized mice, despite comparable antigen-specific CD8+ T cell magnitudes.
[Communications Biology]
Ku, M. W., Authié, P., Nevo, F., Souque, P., Bourgine, M., Romano, M., Charneau, P., & Majlessi, L. (2021). Lentiviral vector induces high-quality memory T cells via dendritic cells transduction. Communications Biology, 4(1), 1–16. https://doi.org/10.1038/s42003-021-02251-6 Cite
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Human Umbilical Cord Mesenchymal Stem Cell Transfusion in Immune Non-Responders with AIDS: A Multicenter Randomized Controlled Trial

The authors examined the safety and efficacy of human umbilical cord mesenchymal stem cell infusion for immune non-responder patients with chronic HIV-1 infection, who represented an unmet medical need even in the era of efficient antiretroviral therapy.
[Signal Transduction and Targeted Therapy]
Wang, L., Zhang, Z., Xu, R., Wang, X., Shu, Z., Chen, X., Wang, S., Liu, J., Li, Y., Wang, L., Zhang, M., Yang, W., Wang, Y., Huang, H., Tu, B., Liang, Z., Li, L., Li, J., Hou, Y., … Wang, F.-S. (2021). Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS: a multicenter randomized controlled trial. Signal Transduction and Targeted Therapy, 6(1), 1–8. https://doi.org/10.1038/s41392-021-00607-2 Cite
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WSX1 Act as a Tumor Suppressor in Hepatocellular Carcinoma by Downregulating Neoplastic PD-L1 Expression

Mechanistically, WSX1 transcriptionally downregulated an isoform of PI3K—PI3Kδ and thereby inactivated AKT, reducing AKT-induced GSK3β inhibition.
[Nature Communications]
Wu, M., Xia, X., Hu, J., Fowlkes, N. W., & Li, S. (2021). WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression. Nature Communications, 12(1), 3500. https://doi.org/10.1038/s41467-021-23864-9 Cite
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Deep Spatial Profiling of Human COVID-19 Brains Reveals Neuroinflammation with Distinct Microanatomical Microglia-T Cell Interactions

Researchers interrogated the brain stem and olfactory bulb in COVID-19 patients postmortem using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis and control patients.
[Immunity]
Schwabenland, M., Salié, H., Tanevski, J., Killmer, S., Lago, M. S., Schlaak, A. E., Mayer, L., Matschke, J., Püschel, K., Fitzek, A., Ondruschka, B., Mei, H. E., Boettler, T., Neumann-Haefelin, C., Hofmann, M., Breithaupt, A., Genc, N., Stadelmann, C., Saez-Rodriguez, J., … Bengsch, B. (2021). Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T cell interactions. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.06.002 Cite
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αSMA+ Fibroblasts Suppress Lgr5+ Cancer Stem Cells and Restrain Colorectal Cancer Progression

Scientists demonstrated that αSMA+ cancer-associated fibroblast in colorectal cancer (CRC) exert tumor-restraining functions via BMP4/TGFβ1 paracrine signaling that served to suppress Lgr5+ CSCs and promoted anti-tumor immunity, ultimately limiting CRC progression.
[Oncogene]
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