Article
Virology
Jing Lu, Jiayuan Jia, Jiahui Zhang, Xinqi Liu
Summary: Nutrient starvation and autophagy upregulation are common responses during T cell activation and HIV infection. The HIV p17 protein inhibits autophagy in T cells under glucose starvation conditions by disrupting cellular complexes, leading to an increased proliferation of HIV-infected cells. This inhibition of autophagy also benefits HIV replication.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Immunology
Elisa Saccon, Flora Mikaeloff, Pol Figueras Ivern, Akos Vegvari, Anders Sonnerborg, Ujjwal Neogi, Robert van Domselaar
Summary: Untreated HIV-1 infection leads to a decrease in CD4(+) T cell lymphocytes, susceptibility to opportunistic infections, and ultimately death. This study found that cytotoxic lymphocytes can target the HIV-1 Gag protein through granzyme cleavage to potentially control HIV-1 infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Nadia Madrid-Elena, Sergio Serrano-Villar, Carolina Gutierrez, Beatriz Sastre, Matias Morin, Laura Luna, Laura Martin, Javier Santoyo-Lopez, Maria Rosa Lopez-Huertas, Elena Moreno, Maria Laura Garcia-Bermejo, Miguel Angel Moreno-Pelayo, Santiago Moreno
Summary: This study demonstrates that modulation of miRNA expression in T cells enhances specific cytotoxic immune responses to HIV, providing a new approach for achieving HIV remission.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Antonella Bugatti, Francesca Caccuri, Federica Filippini, Cosetta Ravelli, Arnaldo Caruso
Summary: This study reveals that HIV-infected cells can secrete B-cell growth-promoting vp17s through proteolytic cleavage. The binding of Pr55(Gag) to phosphatidylinositol-(4,5)-bisphosphate is essential for the unconventional secretion of vp17s. Discovery of heparan sulfate proteoglycans involvement in tethering p17s at the cell surface opens new possibilities for immune-mediated killing of HIV-1 reservoirs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Karolin I. Wagner, Laura M. Mateyka, Sebastian Jarosch, Vincent Grass, Simone Weber, Kilian Schober, Monika Hammel, Teresa Burrell, Behnam Kalali, Holger Poppert, Henriette Beyer, Sophia Schambeck, Stefan Holdenrieder, Andrea Strotges-Achatz, Verena Haselmann, Michael Neumaier, Johanna Erber, Alina Priller, Sarah Yazici, Hedwig Roggendorf, Marcus Odendahl, Torsten Tonn, Andrea Dick, Klaus Witter, Hrvoje Mijocevic, Ulrike Protzer, Percy A. Knolle, Andreas Pichlmair, Claudia S. Crowell, Markus Gerhard, Elvira D'Ippolito, Dirk H. Busch
Summary: This study isolated TCR repertoires specific for SARS-CoV-2 epitopes restricted to common HLA class I molecules in convalescent individuals. SARS-CoV-2-specific CD8(+) T cells were found to be detectable up to 12 months after infection. The TCR repertoires were diverse, with heterogeneous functional avidity and cytotoxicity towards virus-infected cells.
Article
Biochemistry & Molecular Biology
Orian Gilmer, Elodie Mailler, Jean-Christophe Paillart, Assia Mouhand, Carine Tisne, Johnson Mak, Redmond P. Smyth, Roland Marquet, Valerie Vivet-Boudou
Summary: Maturation of HIV-1 viral particles is essential for infectivity. While the structural rearrangements of viral proteins during maturation are well-known, the maturation of genomic RNA (gRNA) structure is less explored. This study investigates the interactions between Pr55(Gag) or its maturation products and the gRNA region, revealing their distinct contributions to gRNA structural maturation.
Article
Immunology
Alex Olvera, Samandhy Cedeno, Anuska Llano, Beatriz Mothe, Jorge Sanchez, Gemma Arsequell, Christian Brander
Summary: Post-translational protein modifications, particularly glycosylation, may impact T cell epitope recognition presented by HLA molecules, but this aspect has been overlooked in HIV research. Studies demonstrated that glycosylation can affect T cell recognition of viral peptides in individuals with chronic HIV infection, indicating the potential importance of glyco-epitope specific T cell immunity in understanding host immune responses against viral infections. New methodologies are needed to accurately assess the role of glycosylation in altering T cell immunity to viral infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Miriam Lisci, Philippa R. Barton, Lyra O. Randzavola, Claire Y. Ma, Julia M. Marchingo, Doreen A. Cantrell, Vincent Paupe, Julien Prudent, Jane C. Stinchcombe, Gillian M. Griffiths
Summary: This study revealed that CTLs require mitochondria for target cell-killing, and this requirement is linked to mitochondrial translation. Inhibition of mitochondrial translation impairs CTL killing by triggering attenuated cytosolic translation, leading to a reduced capacity for sustained killing. Mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing.
Article
Oncology
Jitske van den Bulk, Manon van der Ploeg, Marieke E. Ijsselsteijn, Dina Ruano, Ruud van der Breggen, Rebekka Duhen, Koen C. M. J. Peeters, Arantza Farina-Sarasqueta, Els M. E. Verdegaal, Sjoerd H. van der Burg, Thomas Duhen, Noel F. C. C. de Miranda
Summary: Expression of CD103 and CD39 can specifically identify neoantigen-specific CD8(+) T cells in colorectal cancers (CRCs) with low mutation burden.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Microbiology
Alice Duchon, Steven Santos, Jianbo Chen, Matthew Brown, Olga A. Nikolaitchik, Sheldon Tai, Jeffrey A. Chao, Eric O. Freed, Vinay K. Pathak, Wei-Shau Hu
Summary: HIV-1 Gag selects and packages the HIV RNA genome during virus assembly, with multimerization and plasma membrane anchoring properties playing critical roles in efficient genome packaging. Studying these properties can provide insights into the mechanisms of viral RNA packaging and assembly of infectious virions.
Article
Biotechnology & Applied Microbiology
Piriya Luangwattananun, Wannasiri Chiraphapphaiboon, Chanitra Thuwajit, Mutita Junking, Pa-Thai Yenchitsomanus
Summary: This study explores the potential of T lymphocytes activated by SmartDC-FR alpha as a treatment for FR alpha-expressing breast cancer. The results show that these activated T lymphocytes exhibit enhanced cytotoxicity against FR alpha-expressing breast cancer cells. This finding provides a new approach for utilizing ACT in the treatment of FR alpha-expressing breast cancer.
Article
Immunology
Arne Knoerck, Gertrud Schaefer, Dalia Alansary, Josephine Richter, Lorenz Thurner, Markus Hoth, Eva C. Schwarz
Summary: This study developed a FRET-based single cell fluorescent assay to compare the cytotoxic efficiency of effector memory CD8(+) T cells (T-EM) and central memory CD8(+) T cells (T-CM). The results showed that T-EM had higher cytotoxic efficiency compared to T-CM. This could be attributed to the higher expression levels of perforin and granzyme B in T-EM, which likely mediate the higher cytotoxic efficiency.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sebastien Walchli, Magdalena Winiarska, Radoslaw Zagozdzon
Summary: This study provides new information on the efficacy of PD-L1-targeted CAR against PD-L1(low) targets. The results show that PD-L1-CAR cells have strong reactivity and cytotoxicity against both PD-L1(high) and PD-L1(low) target cells. Additionally, PD-L1-CAR cells also exhibit potent cytotoxic effects against non-malignant cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Microbiology
Jerome Kervevan, Aurelie Bouteau, Juliane S. Lanza, Adele Hammoudi, Sandra Zurawski, Mathieu Surenaud, Lydie Dieudonne, Marion Bonnet, Cecile Lefebvre, Hakim Hocini, Romain Marlin, Aurelie Guguin, Barbara Hersant, Oana Hermeziu, Elisabeth Menu, Christine Lacabaratz, Jean-Daniel Lelievre, Gerard Zurawski, Veronique Godot, Sandrine Henri, Botond Z. Igyarto, Yves Levy, Sylvain Cardinaud
Summary: Targeting of skin Langerhans cells (LC) may efficiently induce potent anti-HIV immune responses, serving as a promising strategy for developing effective HIV-1 vaccines. This approach demonstrates the potential of directing immune responses through specific cell targeting and may lead to the induction of protective antibodies against HIV-1.
Article
Oncology
Sheng Wang, Maohua Huang, Minfeng Chen, Zhiting Sun, Yubo Jiao, Geni Ye, Jinghua Pan, Wencai Ye, Jianfu Zhao, Dongmei Zhang
Summary: This study found that the combination therapy of androgen deprivation therapy (ADT) with zoledronic acid (ZA) and thymosin α1 (Tα1) improved the therapeutic outcomes of patients with prostate cancer (PCa) by enhancing antitumor immunity. ZA and Tα1 treatment inhibited the growth of immune cold PCa tumors, increased the infiltration of cytotoxic CD8(+) T cells, and stimulated pro-inflammatory macrophages. This research paves the way for the application of ZA plus Tα1 therapy as an immunotherapeutic strategy for treating immune unresponsive PCa patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Laura Gehrcken, Tatjana Sauerer, Niels Schaft, Jan Doerrie
Summary: Merkel cell carcinoma is a rare and aggressive skin cancer, predominantly caused by Merkel cell polyomavirus or UV light. Checkpoint inhibitor therapies like PD-1/PD-L1 inhibitors show promise in treating metastatic MCC, but some patients do not respond due to diverse immune-related adverse events caused by various mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Naomi C. Bosch, Lena-Marie Martin, Caroline J. Voskens, Carola Berking, Barbara Seliger, Gerold Schuler, Niels Schaft, Jan Doerrie
Summary: NK cells play a crucial role in tumor cell rejection, and activating NK cells along with other immune cells can lead to a more comprehensive cellular response. Dendritic cells are capable of enhancing immune responses by activating NK cells and producing IL-12, while IL-15 serves as an important NK cell activator as well.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Stefanie Hoyer, Valentina Eberlein, Gerold Schuler, Carola Berking, Lucie Heinzerling, Niels Schaft, Jan Doerrie
Summary: This study investigated the impact of BRAFi/MEKi on the maturation of monocyte-derived dendritic cells (moDCs) and their interaction with T cells. The findings showed that these inhibitors altered cytokine secretion and surface marker expression of DCs, leading to lower activation markers and cytokine secretion in T cells during antigen-specific stimulation。
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Astrid Strack, Andrea Deinzer, Christian Thirion, Silke Schroedel, Jan Doerrie, Tatjana Sauerer, Alexander Steinkasserer, Ilka Knippertz
Summary: In this study, the use of LentiBOOST(R)/Polybrene significantly improved the transduction rate of HAdV-5 in various immune cells in both mice and humans, without affecting their phenotype and function.
Article
Immunology
Elias A. T. Koch, Niels Schaft, Mirko Kummer, Carola Berking, Gerold Schuler, Kenichiro Hasumi, Jan Doerrie, Beatrice Schuler-Thurner
Summary: Uveal melanoma is a rare disease with poor response to traditional therapies. Researchers designed a trial using personalized dendritic cell vaccines to activate the immune system and potentially improve clinical outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xin Lai, Christine Keller, Guido Santos, Niels Schaft, Jan Doerrie, Julio Vera
Summary: Dendritic cells (DCs) can be used for therapeutic vaccination against cancer. Computational modeling can improve our understanding of the molecular mechanisms underlying DC-induced CTL response and help identify new strategies to improve therapeutic DC vaccination for cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Amke C. Beenen, Tatjana Sauerer, Niels Schaft, Jan Doerrie
Summary: PD-L1 is a transmembrane protein that plays a crucial role in immune modulation. It interacts with its receptor PD-1 to induce an immune-suppressive signal, regulating the activity of T cells and other effector cells. Apart from its application in cancer therapy, the role of PD-L1 in healthy tissue and non-cancerous diseases has been largely overlooked.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Dennis Christoph Harrer, Charlotte Schenkel, Carola Berking, Wolfgang Herr, Hinrich Abken, Jan Doerrie, Niels Schaft
Summary: In this study, the FDA-approved drug decitabine was used to upregulate the expression of CSPG4 in ovarian carcinoma cells, expanding the repertoire of targetable antigens. The results demonstrated the potential of CSPG4 as an inducible antigen for CAR-T cells in ovarian cancer.
Article
Multidisciplinary Sciences
Lukas Heger, Lukas Hatscher, Chunguang Liang, Christian H. K. Lehmann, Lukas Amon, Jennifer J. Luehr, Tomasz Kaszubowski, Rayk Nzirorera, Niels Schaft, Jan Doerrie, Pascal Irrgang, Matthias Tenbusch, Meik Kunz, Eileen Socher, Stella E. Autenrieth, Ariawan Purbojo, Horia Sirbu, Arndt Hartmann, Christoph Alexiou, Robert Cesnjevar, Diana Dudziak
Summary: Dendritic cells (DCs) are important regulators of immune responses, and can be classified into different types. One type of human DCs, called cDC1, can be distinguished based on the expression of XCR1. XCR1(+) cDC1 have a pre-activated phenotype, secrete high levels of inflammatory cytokines and chemokines upon stimulation, and are efficient in activating NK cells as well as inhibiting replication of Influenza A virus. XCR1(-) cDC1, on the other hand, may represent a late immediate precursor of cDC1 and secrete comparable level of inflammatory cytokines after differentiation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Felix Pfister, Jan Doerrie, Niels Schaft, Vera Buchele, Harald Unterweger, Lucas R. Carnell, Patrick Schreier, Rene Stein, Marketa Kubankova, Jochen Guck, Holger Hackstein, Christoph Alexiou, Christina Janko
Summary: The influence of superparamagnetic iron oxide nanoparticles (SPIONs) on primary human T cells and their potential for magnetically targeted adoptive T cell therapy were investigated in this study. Results showed that SPION-loading did not affect the mechanics and functionality of T cells, indicating its potential for magnetically enriching T cells in solid tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Dennis Christoph Harrer, Jan Doerrie, Niels Schaft
Summary: The development of CAR-T cells has revolutionized cancer immunotherapy, but there are challenges such as relapse or refractory disease in some patients, especially those with solid tumors. Obstacles to successful CAR-T cell therapy include antigen shutdown and CAR-T cell dysfunctionality. This review highlights different approaches, including combining CAR-T cells with drugs, to overcome these obstacles and improve the efficacy of CAR-T cell therapy in both hematological malignancies and solid tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)