Article
Biochemistry & Molecular Biology
Rebecca L. O'Brien, Jennifer Matsuda, M. Kemal Aydintug, Niyun Jin, Swati Phalke, Willi K. Born
Summary: Previous studies have shown inconsistent results regarding the role of gamma delta T cells in the development of type 1 diabetes. This study focused on NOD mice and found that NOD V γ4+ γδ T cells inhibit diabetes development, while NOD V γ1+ cells promote it. Additionally, changes in the abundance of other T cell types were observed in NOD mice deficient in specific gamma delta T cell subsets.
Article
Immunology
Hai Yang, Jason Cham, Brian Patrick Neal, Zenghua Fan, Tao He, Li Zhang
Summary: T cells are important for adaptive immunity and play a role in anti-tumoral immunity and defense against infections, including respiratory viruses like SARS-CoV-2. A customized pipeline for Network Analysis of Immune Repertoire (NAIR) was developed to analyze T-cell receptor (TCR) sequences. Network analysis and statistical methods were used to characterize the repertoire and correlate it with clinical outcomes. Disease-specific/associated clusters and shared clusters were identified, and a new metric incorporating clonal generation probability and clonal abundance was used to identify disease-specific TCRs. The proposed approach revealed potential disease-specific TCRs responsible for the immune response to COVID-19.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Yizhe Li, Jian Hu, Yongsi Wang, Dongdong Liu, Yaling Shi, Jiaqi Zhang, Yuntao Liu, Dongzi Lin, Jing Lin, Wei Hu, Haolan He, Wei Wang, Wentao Fan, Linlin Li, Dawei Wang, Kejian Wang, Jianhua Xu
Summary: By analyzing the peripheral T-cell receptor repertoire of 54 COVID-19 patients, a set of characteristic gene combinations were identified to distinguish asymptomatic and symptomatic patients, and predict the risk of recurrence in re-detectable positive cases. These findings have the potential to strengthen clinical surveillance and the development of immunotherapy for COVID-19.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Samuele Notarbartolo, Valeria Ranzani, Alessandra Bandera, Paola Gruarin, Valeria Bevilacqua, Anna Rita Putignano, Andrea Gobbini, Eugenia Galeota, Cristina Manara, Mauro Bombaci, Elisa Pesce, Elena Zagato, Andrea Favalli, Maria Lucia Sarnicola, Serena Curti, Mariacristina Crosti, Martina Martinovic, Tanya Fabbris, Federico Marini, Lorena Donnici, Mariangela Lorenzo, Marilena Mancino, Riccardo Ungaro, Andrea Lombardi, Davide Mangioni, Antonio Muscatello, Stefano Aliberti, Francesco Blasi, Tullia De Feo, Daniele Prati, Lara Manganaro, Francesca Granucci, Antonio Lanzavecchia, Raffaele De Francesco, Andrea Gori, Renata Grifantini, Sergio Abrignani
Summary: This study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8(+) T cell population with memory precursor-like features.
SCIENCE IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Aviv Omer, Ayelet Peres, Oscar L. Rodriguez, Corey T. Watson, William Lees, Pazit Polak, Andrew M. Collins, Gur Yaari
Summary: Adaptive immune receptor repertoire sequencing (AIRR-seq) is crucial for studying immune system dynamics. In this study, a B cell pipeline was adapted for genotype and haplotype inference of undocumented alleles in T cell receptor (TCR) data sets. The results revealed a rich picture of germline variability, and showed how a single nucleotide polymorphism dramatically affects the composition of the repertoire.
Article
Pharmacology & Pharmacy
Xueying Li, Anqi Zheng, Jiabang Liu, Mengfen Shi, Baolin Liao, Shi Xie, Rong Yan, Yifan Gan, Xuan Zuo, Mingxing Gong, Hongkai Wu, Zhanhui Wang
Summary: Challenges still exist in assessing HBV-specific T cell immunity in chronic hepatitis B patients, including the need for large quantities of cells. In this study, a dataset of HBV-specific T cell receptor beta chains (TCR beta s) was established using public databases and samples from acute hepatitis B patients. Analysis of the potential HBV-specific TCR beta s from chronic hepatitis B patients showed that individuals with better therapy response may rely more on newly emerging TCR beta s. Furthermore, the characteristics of potential HBV-specific clusters were found to differ between chronic hepatitis B and hepatocellular carcinoma patients in a cross-sectional study. Our strategy provides a convenient method for assessing HBV-specific T cell immunity using a small blood sample.
ANTIVIRAL RESEARCH
(2023)
Article
Immunology
Achia Khatun, Moujtaba Y. Kasmani, Ryan Zander, David M. Schauder, Jeremy P. Snook, Jian Shen, Xiaopeng Wu, Robert Burns, Yi-Guang Chen, Chien-Wei Lin, Matthew A. Williams, Weiguo Cui
Summary: Single-cell sequencing technology was used to track individual virus-specific CD4 T cells during an acute lymphocytic choriomeningitis virus (LCMV) infection, revealing previously unappreciated clonal diversity and cellular heterogeneity among virus-specific helper T cells. Despite most naive CD4 T cells giving rise to multiple lineages, approximately 28% of naive cells exhibited a preference towards either Th1 or T-FH cells, with the TCR structure influencing lineage decisions.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Tara K. Sigdel, Paul A. Fields, Juliane Liberto, Izabella Damm, Maggie Kerwin, Jill Hood, Parhom Towfighi, Marina Sirota, Harlan S. Robins, Minnie M. Sarwal
Summary: In this study, researchers analyzed the T-cell repertoire in kidney transplant recipients and found that changes in the repertoire are associated with post-transplant rejection episodes. T-cell receptor sequencing may serve as a valuable tool for predicting rejection risk after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Seon Ah Lim, Wei Su, Nicole M. Chapman, Hongbo Chi
Summary: T cells play a crucial role in immune response and can regulate the development of cancer and autoimmune diseases. Lipid metabolism is a key regulator of T cell function and fate decision, integrating environmental signals and intracellular signaling processes. This article discusses the roles of extracellular, de novo synthesized and membrane lipids in T cell biology, as well as their role as regulators of intracellular signaling. Therapeutic targeting of lipid metabolism and signaling is also summarized, with important future directions discussed.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Akshay J. Patel, Zena N. Willsmore, Naeem Khan, Alex Richter, Babu Naidu, Mark T. Drayson, Sophie Papa, Andrew Cope, Sophia N. Karagiannis, Esperanza Perucha, Gary W. Middleton
Summary: Checkpoint blockade with Pembrolizumab has proven effective in treating advanced non-small cell lung cancer. However, some patients experience high-grade immune related adverse events (irAEs) during treatment. This study reveals that a deficient Breg checkpoint fails to control self-reactive T cell activity and auto-antibody formation in these patients, leading to severe auto-inflammatory sequelae. Pre-therapy B cell profiling may help identify patients at high risk of developing severe irAEs.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Ksenia V. Zornikova, Saveliy A. Sheetikov, Alexander Yu Rusinov, Rustam N. Iskhakov, Apollinariya V. Bogolyubova
Summary: The T cell response is crucial for controlling and clearing SARS-CoV-2 infection. However, there are still important questions regarding the role of cellular immunity in COVID-19, such as the characteristics of disease-specific T cell repertoires in convalescent patients and vaccinated individuals, and how T cell responses to other pathogens, particularly common cold coronaviruses, affect susceptibility to SARS-CoV-2 infection and disease progression. This review focuses on the shaping of T cell receptor (TCR) repertoires by natural infection and vaccination, cross-reactive T cell responses, and the implications of TCR repertoire diversity and cross-reactivity for the development of vaccines that can provide broad protection against SARS-CoV-2 variants.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yaroslav Kaminskiy, Jan Joseph Melenhorst
Summary: This review summarizes the role of STAT3 in the formation of memory T cells and antitumor immunity, highlighting its crucial role in long-term T cell immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Hu-Qin Yang, Yi-Shan Wang, Kan Zhai, Zhao-Hui Tong
Summary: This study found that mice infected with Pneumocystis demonstrated reduced TCR diversity in CD4(+) T cells and increased diversity in CD8(+) T cells. Th17 cells were mainly composed of CD4(+) T cells and exhibited the phenotype of tissue-resident memory-like Th17 cells. Additionally, Pneumocystis-infected mice showed biased usage of TCR beta VDJ genes.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Oncology
Nicla Porciello, Ornella Franzese, Lorenzo D'Ambrosio, Belinda Palermo, Paola Nistico
Summary: Profiling the T-cell receptor repertoire allows for the investigation of antitumor immune response. By tracking the spatiotemporal variation of T-cell populations, the key cells responsible for tumor eradication can be identified. Furthermore, improvements in T-cell sequencing provide new opportunities and challenges for research.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Oncology
Winnie Yao, Ansuman T. Satpathy
Summary: Transient depletion of CD4(+) T cells in patients with gastrointestinal cancer induces remodeling of the T-cell repertoire, including clonal replacement and expansion of CD8(+) T-cell clones shared between the blood and tumor, deepening our understanding of tumor-specific CD8(+) T-cell responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Rebecca J. Lee, Oskar Wysocki, Cong Zhou, Rohan Shotton, Ann Tivey, Louise Lever, Joshua Woodcock, Laurence Albiges, Angelos Angelakas, Dirk Arnold, Theingi Aung, Kathryn Banfill, Mark Baxter, Fabrice Barlesi, Arnaud Bayle, Benjamin Besse, Talvinder Bhogal, Hayley Boyce, Fiona Britton, Antonio Calles, Luis Castelo-Branco, Ellen Copson, Adina E. Croitoru, Sourbha S. Dani, Elena Dickens, Leonie Eastlake, Paul Fitzpatrick, Stephanie Foulon, Henrik Frederiksen, Hannah Frost, Sarju Ganatra, Spyridon Gennatas, Andreas Glenthoj, Fabio Gomes, Donna M. Graham, Christina Hague, Kevin Harrington, Michelle Harrison, Laura Horsley, Richard Hoskins, Prerana Huddar, Zoe Hudson, Lasse H. Jakobsen, Nalinie Joharatnam-Hogan, Sam Khan, Umair T. Khan, Khurum Khan, Christophe Massard, Alec Maynard, Hayley McKenzie, Olivier Michielin, Anne C. Mosenthal, Berta Obispo, Rushin Patel, George Pentheroudakis, Solange Peters, Kimberly Rieger-Christ, Timothy Robinson, Jacobo Rogado, Emanuela Romano, Michael Rowe, Marina Sekacheva, Roseleen Sheehan, Julie Stevenson, Alexander Stockdale, Anne Thomas, Lance Turtle, David Vinal, Jamie Weaver, Sophie Williams, Caroline Wilson, Carlo Palmieri, Donal Landers, Timothy Cooksley, Caroline Dive, Andre Freitas, Anne C. Armstrong
Summary: The study aimed to develop a decision support tool to assist in hospital admission decisions and predict the severity of COVID-19 in cancer patients. The results showed that the CORONET model could effectively predict the need for hospital admission and the severity of the disease, and it was validated in healthcare systems worldwide.
JCO CLINICAL CANCER INFORMATICS
(2022)
Article
Oncology
Claus Garbe, Ulrike Keim, Teresa Amaral, Carola Berking, Thomas K. Eigentler, Lukas Flatz, Anja Gesierich, Ulrike Leiter, Rudolf Stadler, Cord Sunderkotter, Thomas Tuting, Jochen Utikal, Uwe Wollina, Lisa Zimmer, Christos C. Zouboulis, Paolo A. Ascierto, Alexander M. M. Eggermont, Jean-Jacques Grob, Axel Hauschild, Lidija Kandolf Sekulovic, Georgina Long, Jason J. Luke, Olivier Michielin, Ketty Peris, Dirk Schadendorf, John M. Kirkwood, Paul C. Lorigan
Summary: This study evaluates the survival probabilities of patients with stage I and II melanoma and finds that the melanoma-specific survival rates in the two cohorts are less favorable compared to the published AJCCv8 data.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ute F. Roehrig, Somi Reddy Majjigapu, Pierre Vogel, Aline Reynaud, Florence Pojer, Nahzli Dilek, Patrick Reichenbach, Kelly Ascencao, Melita Irving, George Coukos, Olivier Michielin, Vincent Zoete
Summary: This study presents an extension of a highly efficient IDO1 inhibitor series, with the best compound showing strong inhibitory effects at both enzymatic and cellular levels. The research provides enzymatic inhibition data for nearly 100 new compounds and X-ray diffraction data for one compound in complex with IDO1, shedding light on the mechanisms behind the drop in activity observed in diverse haem-binding inhibitor scaffolds when extended to pocket B. These findings offer valuable insights for the future design of IDO1 inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Letter
Hematology
David Gachoud, Claire Bertelli, Nathalie Rufer
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Nathalie Testart Dardel, Elsa Isenborghs, Massimo Valerio, Olivier Michielin, Niklaus Schaefer
Summary: This case demonstrates an unusual presentation of melanoma metastasis in the right seminal vesicle, detected by F-18-FDG digital PET/CT. Histological analysis confirmed the diagnosis and the patient received stereotactic radiation therapy. The study highlights the excellent performance of state-of-the-art digital PET/CT and emphasizes the importance of a multidisciplinary approach in the treatment and follow-up of melanoma patients.
CLINICAL NUCLEAR MEDICINE
(2023)
Article
Chemistry, Organic
Loris Laze, Paula Romero, Irene Bosque, Jose C. Gonzalez-Gomez
Summary: This study presents an efficient method for the regioselective C-3-H/C-3-H cross-coupling of 4-hydroxycoumarin derivatives with quinoxalin-2(1H)-ones, using visible light and air as the terminal oxidant. The reaction is promoted by sunlight under mild and sustainable conditions, and the C-4-OH group at the coumarin ring is essential for the reaction and allows for diversified functionalizations of the final products. The greenness of this methodology over previous ones is demonstrated through qualitative and semi-quantitative analysis, and a plausible mechanism for this transformation is proposed through various experiments.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Oncology
Bianca Gautron Moura, Camille L. Gerard, Nathalie Testart, Marian Caikovski, Alexandre Wicky, Veronica Aedo-Lopez, Gregoire Berthod, Krisztian Homicsko, John O. Prior, Clarisse Dromain, Lana E. Kandalaft, Michel A. Cuendet, Olivier Michielin
Summary: In stage IV melanoma, the combination of ipilimumab and nivolumab significantly improves outcomes but has a major financial impact on healthcare. This study analyzes the costs associated with ipilimumab-nivolumab combination, focusing on immune-related adverse events (irAE). Surprisingly, toxicity costs are insignificant compared to the total treatment costs, and patients with higher toxicity grades have lower costs and better outcomes. These findings provide important information for clinicians and healthcare organizations making treatment decisions in immunotherapy.
Letter
Hematology
Mathilde Gavillet, Nathalie Rufer, Francesco Grandoni, Mattia Rizzi, Nicolas Vulliemoz, David Baud, Lorenzo Alberio, Giorgia Canellini, Helene Legardeur
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Sandro Anchisi, Anita Wolfer, Bettina Bisig, Edoardo Missiglia, Amine Tiab, Ehab Mohamed Kamel, Olivier Michielin, George Coukos, Krisztian Homicsko
Summary: The treatment of BRAFV600E mutant melanoma has been revolutionized by BRAF inhibitors, and BRAF/MEK combination has shown further improvements. BRAF inhibitor use has also been proposed in low-grade ovarian tumors.
CANCER BIOLOGY & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Fanny Seraphine Krebs, Bianca Moura, Edoardo Missiaglia, Veronica Aedo-Lopez, Olivier Michielin, Petros Tsantoulis, Bettina Bisig, Mounir Trimech, Vincent Zoete, Krisztian Homicsko
Summary: The development of targeted therapies for non-BRAF p.Val600-mutant melanomas remains challenging as Triple wildtype (TWT) melanomas lacking BRAF, NRAS, or NF1 mutations are heterogeneous in their genomic drivers. MAP2K1 mutations are enriched in BRAF-mutant melanomas and function as resistance mechanisms to BRAF inhibition. This case study illustrates the difficulties in combining MEK1 and CDK4/6 inhibitors in the presence of resistance to MEK inhibitor monotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alexandre Wicky, Roberto Gatta, Sofiya Latifyan, Rita De Micheli, Camille Gerard, Sylvain Pradervand, Olivier Michielin, Michel A. Cuendet
Summary: The increasing availability of clinical real-world data (RWD) provides an opportunity to supplement evidence from randomized clinical trials and explore treatment outcomes in real-life conditions. Process mining is a suitable methodology for analyzing treatment paths and outcomes. In this study, an interactive application was implemented to compare treatment sequences based on overall survival, progression-free survival, and best overall response. The application was used to conduct a descriptive analysis of RWD in advanced melanoma patients and explore the outcomes of different treatment choices. Results showed long-term survival benefits from immune-checkpoint inhibitors rechallenge, suggesting potential implications for treatment guidelines.
FRONTIERS IN ONCOLOGY
(2023)
Meeting Abstract
Medicine, General & Internal
A. Da Silva Lopes, S. Colomer-Lahiguera, C. Darnac S. Giacomini, A. Wicky, S. Bugeia, G. Gutknecht, N. Mederos Alfonso, S. Latifyan, A. Addeo, O. Michielin, M. Eicher
SWISS MEDICAL WEEKLY
(2022)
Correction
Oncology
O. Michielin, A. Lalani, C. Robert
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Health Care Sciences & Services
Victoria Federico Paly, Murat Kurt, Lirong Zhang, Marcus O. Butler, Olivier Michielin, Adenike Amadi, Emma Hernlund, Helen M. Johnson, Srividya Kotapati, Andriy Moshyk, John Borrill
Summary: This study evaluated the predictive accuracy of different models in estimating the long-term overall survival benefit of immune checkpoint inhibitor combination therapy in advanced melanoma. The results showed that models explicitly incorporating survival heterogeneity provided more accurate and consistent long-term overall survival estimates.
MDM POLICY & PRACTICE
(2022)
Article
Oncology
Krisztian Homicsko, Reinhard Dummer, Christoph Hoeller, Jedd D. Wolchok, F. Stephen Hodi, James Larkin, Paolo A. Ascierto, Victoria Atkinson, Caroline Robert, Michael A. Postow, Sandra Re, David Paulucci, Darin Dobler, Olivier Michielin
Summary: This retrospective analysis examined the impact of proton pump inhibitors (PPIs) on the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. The results showed insufficient evidence to support a meaningful association between PPI use and ICI efficacy.