Article
Multidisciplinary Sciences
Tamara Verkerk, Sofie J. Koomen, Kyra J. Fuchs, Marieke Griffioen, Robbert M. Spaapen
Summary: In the era of T cell-based immunotherapies, understanding the types of MHC-presented T cell antigens produced by tumor cells is crucial. This Perspective highlights the significance of knowing the contribution of chimeric peptides generated through proteasome-catalyzed peptide splicing (PCPS) and reviews methodologies for identifying MHC-presented spliced peptide antigens. The analysis shows that spliced peptides make only a marginal contribution to the pool of immunogenic tumor antigens, suggesting that they may not be a comprehensive source for expanding the number of targetable antigens in immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Ines Marin, Olga Boix, Andrea Garcia-Garijo, Isabelle Sirois, Adria Caballe, Eduardo Zarzuela, Irene Ruano, Camille Stephan-Otto Attolini, Neus Prats, Jose A. Lopez-Dominguez, Marta Kovatcheva, Elena Garralda, Javier Munoz, Etienne Caron, Maria Abad, Alena Gros, Federico Pietrocola, Manuel Serrano
Summary: Senescent cells possess various features that make them highly efficient in stimulating dendritic cells and antigen-specific CD8 T cells, including the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of specific self-peptides. Immunization with senescent cancer cells induces strong antitumor protection mediated by DCs and CD8 T cells, surpassing the effectiveness of immunization with cancer cells undergoing immunogenic cell death. Furthermore, induction of senescence in human primary cancer cells enhances their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. This study highlights the potential of exploiting senescent cancer cells to develop efficient and protective CD8-dependent antitumor immune responses.
Article
Cell Biology
Xi Cao, Xingtong Zhou, Chang Chen, Zhe Wang, Qiang Sun
Summary: This study identified potential antigens CCNE1 and PLK1 in breast cancer and an ICD-related prognostic model that distinguished immune response heterogeneity and predicted prognosis. Patients with high ICD-related risk scores were suitable for combination treatments based on CCNE1 or PLK1 and immune checkpoint inhibitors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Chiao-Hsu Ke, Yi-Han Chiu, Kuo-Chin Huang, Chen-Si Lin
Summary: The mechanisms of immunosurveillance, the process by which immune systems identify and destroy tumors, have been studied for decades. However, factors such as immunoediting and the exploitation of inhibitory cytokines by tumors have been found to allow them to evade immune surveillance. Autologous cancer vaccines (ACVs), which contain enriched tumor antigens, have been proposed as a potential immunotherapy, but their low immunogenicity limits their effectiveness. The restructuring of tumor antigens and combinational therapy to reverse suppressive tumor microenvironments show promise in improving the efficacy of ACVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Ashley R. Hoover, Saghar Kaabinejadian, Jason R. Krawic, Xiao-Hong Sun, Abdul Rafeh Naqash, Qian Yin, Xinbo Yang, K. Christopher Garcia, Mark M. Davis, William H. Hildebrand, Wei R. Chen
Summary: The study demonstrates that laser immunotherapy (LIT) enhances the activation of T cells and drives de novo antitumor T-cell responses. LIT stimulates a stronger and more consistent antitumor T-cell response to immunologically "cold" tumors and confers long-term antitumor memory on tumor rechallenge.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Sourat Darabi, Andrew Elliott, David R. Braxton, Jia Zeng, Kurt Hodges, Kelsey Poorman, Jeff Swensen, Basavaraja U. Shanthappa, James P. Hinton, Geoffrey T. Gibney, Justin Moser, Thuy Phung, Michael B. Atkins, Gino K. In, Wolfgang M. Korn, Burton L. Eisenberg, Michael J. Demeure
Summary: Malignant melanoma is a complex disease with a high mortality rate. Recent molecular studies have identified gene fusions in melanomas, which may serve as therapeutic targets. However, more research is needed to fully understand the implications and effectiveness of targeting these fusions.
Article
Engineering, Biomedical
Ping Ji, Xin-Chen Deng, Xiao-Kang Jin, Shi-Man Zhang, Jia-Wei Wang, Jun Feng, Wei-Hai Chen, Xian-Zheng Zhang
Summary: A tumor-specific nanovaccine, named FCM@4RM, is designed to deliver tumor antigens and adjuvants to antigen-presenting cells and modulate the immune microenvironment for strong antitumor immunity. This nanovaccine shows high targeting capabilities towards tumors developed from 4T1 cells, providing a paradigm for developing nanovaccines that systematically regulate multiple immune-related processes for optimal antitumor immunotherapy.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Virology
Rekha Dhanwani, Sandeep Kumar Dhanda, John Pham, Gregory P. Williams, John Sidney, Alba Grifoni, Gaelle Picarda, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Chris A. Benedict
Summary: This study systematically analyzed the CMV ORFeome to identify new CMV epitopes targeted primarily by CD4 T cells in humans, identifying over 200 new T cell epitopes derived from both canonical and novel ORFs. The findings highlight the substantial breadth of the anti-CMV T cell response and provide new targets for vaccine design.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Valeria Ukrainskaya, Yuri Rubtsov, Dmitry Pershin, Nadezhda Podoplelova, Stanislav Terekhov, Igor Yaroshevich, Anstasiia Sokolova, Dmitry Bagrov, Elena Kulakovskaya, Victoria Shipunova, Sergey Deyev, Rustam Ziganshin, Aleksandr Chernov, Georgii Telegin, Eugene Maksimov, Oleg Markov, Anastasiya Oshchepkova, Marina Zenkova, Jia Xie, Hongkai Zhang, Alexander Gabibov, Michael Maschan, Alexey Stepanov, Richard Lerner
Summary: The development of CAR-T therapy has achieved success in the treatment of B cell leukemia, but the expansion of CAR-T cells remains challenging with current protocols. A novel approach using cell-derived membrane vesicles has been proposed, showing greater potential in stimulating, proliferating, and enhancing the functional activity of CAR-T cells.
Article
Multidisciplinary Sciences
Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lonnberg, Anna Kreutzman, Katriina Peltola, Micaela Hernberg, Chunlin Wang, Cassian Yee, Harri Lahdesmaki, Mark M. Davis, Satu Mustjoki
Summary: Analyzing T cell receptor (TCR) repertoire data from melanoma patients and healthy controls, we discovered the significance of antigen-specific T cells in distinguishing patients and predicting metastatic recurrence. These findings provide insights into human disorders.
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Xiaoding Liu, Xianglin Yin, Dongmei Li, Kaimi Li, Hui Zhang, Junliang Lu, Liangrui Zhou, Jie Gao, Jing Wang, Huanwen Wu, Zhiyong Liang
Summary: This study investigated fusion genes in 76 cases of PMTs using RNA-based next-generation sequencing. It was found that 68.4% of the cases had fusion genes, and the most common fusion was FN1::FGFR1. Moreover, novel fusion genes were also identified. These findings are important for understanding the genetic basis of PMTs.
Article
Oncology
Rasmus Erik Johansson Mortensen, Morten Orebo Holmstrom, Thomas Landkildehus Lisle, Jane P. Hasselby, Gro L. Willemoe, Ozcan Met, Inge Marie Svane, Julia Johansen, Dorte L. Nielsen, Inna M. Chen, Mads Hald Andersen
Summary: This study investigated the significance of TGF-beta-specific T-cell immunity in patients with pancreatic cancer treated with ICI combined with radiotherapy. The results showed that patients with a strong TGF-beta-specific immune response had longer progression-free and overall survival compared to those with a weak or no response. It was also found that TGF-beta-specific T cells could recognize and enhance immune responses. Thus, combining TGF-beta vaccination with ICI/radiotherapy may benefit patients with pancreatic cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Camille Jacqueline, Matthew Dracz, Jia Xue, Robert J. Binder, Jonathan Minden, Olivera Finn
Summary: Antibodies and T cells specific for tumor-associated antigens (TAA) were found in individuals without cancer but with a history of infections, suggesting a potential association between immune responses to infections and lowered cancer risk. In a mouse model, mice with a history of lymphocytic choriomeningitis virus (LCMV) infection showed better control of tumors compared to mice without infection history. Vaccination with tumor-derived gp96, a heat shock protein, induced specific immunity against disease-associated antigens (DAA) and tumor-associated antigens (TAA), leading to lower viral copy numbers in infected mice. DAA/TAA may be promising candidates for vaccines against both infections and cancer.
Article
Engineering, Biomedical
Shuang Zeng, Chen Chen, Liuwei Zhang, Xiaosheng Liu, Ming Qian, Hongyan Cui, Jingyun Wang, Qixian Chen, Xiaojun Peng
Summary: By targeting specific subcellular organelles and utilizing photosensitizers, we have successfully activated pyroptosis and immunogenic cell death, which effectively inhibits tumor growth and metastasis. In vivo experiments have demonstrated that this approach not only suppresses the growth of primary tumors but also has an abscopal effect on distant tumors and metastatic tumors.
BIOACTIVE MATERIALS
(2023)
Article
Medicine, Research & Experimental
Katarina Madunic, Oleg A. Mayboroda, Tao Zhang, Julia Weber, Geert-Jan Boons, Hans Morreau, Ronald van Vlierberghe, Tom van Wezel, Guinevere S. M. Lageveen-Kammeijer, Manfred Wuhrer
Summary: Cells are covered with a dense layer of carbohydrates, some of which are solely present on neoplastic cells. The so-called tumor-associated carbohydrate antigens (TACAs) are increasingly recognized as promising targets for immunotherapy. These carbohydrates differ from those of the surrounding non-cancerous tissues and contribute to the malignant phenotype of the cancer cells by promoting proliferation, metastasis, and immunosuppression. However, due to tumor tissue heterogeneity and technological limitations, TACAs are insufficiently explored. In this study, a workflow was established to analyze the colorectal cancer (CRC)-associated O-linked glycans. Distinctive O-glycosylation features were found in cancerous, stromal, and normal colon mucosal regions. Over 100 O-linked glycans were detected in cancerous regions with absence in normal mucosa. A novel panel of highly specific TACAs, based upon differences in the glycomic profiles between CRC and healthy colon mucosa, were identified. These TACAs could be potential targets for innovative cancer immune target therapies and lay the foundation for the targeted treatment of CRC.
Article
Oncology
Barbara Schroers, Sebastian Boegel, Christian Albrecht, Thomas Bukur, Valesca Bukur, Christoph Holtstraeter, Christoph Ritzel, Katja Manninen, Arbel D. Tadmor, Mathias Vormehr, Ugur Sahin, Martin Loewer
FRONTIERS IN ONCOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Daniel K. Wells, Marit M. van Buuren, Kristen K. Dang, Vanessa M. Hubbard-Lucey, Kathleen C. F. Sheehan, Katie M. Campbell, Andrew Lamb, Jeffrey P. Ward, John Sidney, Ana B. Blazquez, Andrew J. Rech, Jesse M. Zaretsky, Begonya Comin-Anduix, Alphonsus H. C. Ng, William Chour, Thomas Yu, Hira Rizvi, Jia M. Chen, Patrice Manning, Gabriela M. Steiner, Xengie C. Doan, Taha Merghoub, Justin Guinney, Adam Kolom, Cheryl Selinsky, Antoni Ribas, Matthew D. Hellmann, Nir Hacohen, Alessandro Sette, James R. Heath, Nina Bhardwaj, Fred Ramsdell, Robert D. Schreiber, Ton N. Schumacher, Pia Kvistborg, Nadine A. Defranoux
Article
Biochemical Research Methods
Franziska Lang, Pablo Riesgo Ferreiro, Martin Loewer, Ugur Sahin, Barbara Schroers
Summary: The study focused on detecting and predicting true neoantigens, leading to the development of an easy-to-use tool called NeoFox for annotating neoantigen candidates with 16 features.
Article
Biochemistry & Molecular Biology
Luisa Bresadola, David Weber, Christoph Ritzel, Martin Loewer, Valesca Bukur, Oezlem Akilli-Oeztuerk, Julia Becker, Hisham Mehanna, Barbara Schroers, Fulvia Vascotto, Ugur Sahin, Anthony Kong
Summary: This study analysed genomic and transcriptomic profiles of three synchronous primary malignancies and a recurrence, finding remarkable heterogeneity among the primary tumors. The origin of the recurrence was traced through shared mutation patterns, and the patient carried germline variants that may predispose to carcinogenesis, along with a history of alcohol and tobacco consumption. Immune cell infiltration analysis revealed an immunosuppressive environment in all samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Franziska Lang, Barbara Schroers, Martin Loewer, Oezlem Tuereci, Ugur Sahin
Summary: This Review discusses the use of tumor-specific neoantigens in anticancer vaccines and introduces the mechanisms of neoantigen T cell recognition, as well as computational approaches to predict which neoantigens might confer proficient antitumor immunity in patients. Individualized treatment approaches are required to harness the full potential of the unique cancer mutations in each patient. Computational algorithms and machine-learning tools can be used to identify mutations, prioritize T cell-recognized antigens, and design personalized vaccines for each patient.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Multidisciplinary Sciences
Barbara Schrors, Pablo Riesgo-Ferreiro, Patrick Sorn, Ranganath Gudimella, Thomas Bukur, Thomas Rosler, Martin Lower, Ugur Sahin
Summary: Research has shown that SARS-CoV-2 spike protein exhibits mutations, with the majority being recurrent variants. While most spike protein mutants have low mutation rates, some variants may impact antibody binding or T-cell recognition. Additionally, high-confidence subclonal variants were identified in around 2.6% of NGS datasets, indicating potential co-infections with various strains and intra-host evolution.
Article
Multidisciplinary Sciences
Leonard Kaps, Anne Huppertsberg, Niklas Choteschovsky, Adrian Klefenz, Feyza Durak, Babara Schroers, Mustafa Diken, Emma Eichler, Sebastian Rosigkeit, Sascha Schmitt, Christian Leps, Alicia Schulze, Friedrich Foerster, Ernesto Bockamp, Bruno G. De Geest, Kaloian Koynov, Hans-Joachim Raeder, Stefan Tenzer, Federico Marini, Detlef Schuppan, Lutz Nuhn
Summary: In this study, liver fibrosis progression was prevented by repolarizing M2-type macrophages towards a non-fibrotic phenotype using a pH-degradable nanogel carrier system. The nanogels efficiently delivered the drug alendronate to nonparenchymal cells of fibrotic livers, reprogramming profibrotic M2 into antifibrotic M1 macrophages and preventing liver fibrosis progression. This approach has potential implications for the treatment of diseases driven by M2-type macrophages, including cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Jian Wang, Tobias Weiss, Marian C. Neidert, Nora C. Toussaint, Reza Naghavian, Carla Selles Moreno, Magdalena Foege, Paula Tomas Ojer, Gioele Medici, Ivan Jelcic, Daniel Schulz, Elisabeth Rushing, Susanne Dettwiler, Barbara Schrors, Joo Heon Shin, Ron McKay, Catherine J. Wu, Andreas Lutterotti, Mireia Sospedra, Holger Moch, Erich F. Greiner, Bernd Bodenmiller, Luca Regli, Michael Weller, Patrick Roth, Roland Martin
Summary: The study developed a strategy to design neopeptides with enhanced immunogenicity through single amino acid mutations. Vaccination with these peptides resulted in immune responses from CD8+ T cells and CD4+ T cells upon tumor recurrence.
CLINICAL CANCER RESEARCH
(2022)
Article
Virology
Thomas Bukur, Pablo Riesgo-Ferreiro, Patrick Sorn, Ranganath Gudimella, Johannes Hausmann, Thomas Roesler, Martin Loewer, Barbara Schroers, Ugur Sahin
Summary: CoVigator is a tool for monitoring SARS-CoV-2 mutations, providing a knowledge base, variant calling, and an interactive dashboard. It can identify and track virus mutations, offering the largest dataset on SARS-CoV-2 intrahost mutations and is available for download.
Article
Immunology
Barbara Schroers, Brett J. Hos, Ikra G. Yildiz, Martin Loewer, Franziska Lang, Christoph Holtstraeter, Julia Becker, Mathias Vormehr, Ugur Sahin, Ferry Ossendorp, Mustafa Diken
Summary: The MC38 cell line, commonly used for colorectal carcinoma studies, has two sub-cell lines (MC38-K and MC38-L) with distinct genomic and transcriptomic differences. CD8+ T cell recognition also varies between the two sub-cell lines. This highlights the importance of accurately selecting the appropriate sub-cell line for research.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Vinzenz Saerchen, Lisa Marie Reindl, Sara Wiedemann, Senthan Shanmugalingam, Thomas Bukur, Julia Becker, Martin Suchan, Evelyn Ullrich, Meike Vogler
Summary: Although pediatric rhabdomyosarcoma (RMS) has shown improved overall survival, the aggressive subtype of alveolar RMS requires new treatment strategies. Researchers found that the use of the Smac mimetic BV6 can sensitize RMS cells to cell death and enhance killing by natural killer (NK) cells. BV6 treatment leads to degradation of inhibitors of apoptosis proteins (IAPs) and activates NF-kappa B signaling pathways in RMS cells. These findings provide insights into the mechanism of BV6 sensitization and suggest potential for combinatory cellular immunotherapy with Smac mimetics.
Article
Oncology
Matthias Birtel, Ralf-Holger Voss, Katharina Reinhard, Benjamin Rengstl, Yasmina Ouchan, Kristina Michel, Nina Hayduk, Bodo Tillmann, Rene Becker, Martin Suchan, Matthias Theobald, Petra Oehm, Oezlem Tuereci, Ugur Sahin
Summary: A novel TCAR T cell was developed, which achieved optimal chain pairing and integration into the T-cell CD3 signaling complex, resulting in enhanced antigen sensitivity and antigen-specific T-cell effector functions. Provision of costimulatory signals and combination with a nanoparticulate RNA vaccine further improved persistence, functionality, and antitumor efficacy of TCAR T cells.
CANCER RESEARCH COMMUNICATIONS
(2022)
