Review
Immunology
Karolina D. Witt
Summary: MHC class I antigen processing is a less recognized area in nonviral host-pathogen interactions, involving immunology and cell biology. This review focuses on the MHC-I antigen processing pathway and alternative sources of antigens, particularly in the context of Mycobacterium tuberculosis (Mtb) as an intracellular pathogen. It explores how Mtb manipulates host immunity for survival and proposes directions for MHC-I-focused approaches in developing vaccines against tuberculosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
M. L. M. Jongsma, J. Neefjes, R. M. Spaapen
Summary: MHC-I molecules present a blueprint of the intracellular proteome to T cells for immune response, but pathogens and tumor cells can downmodulate MHC-I mediated antigen presentation to evade immune surveillance. While the fundamental rules of antigen presentation are well understood, new modules of regulation in this system continue to be uncovered.
MOLECULAR IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jeff D. Colbert, Freidrich M. Cruz, Christina E. Baer, Kenneth L. Rock
Summary: This study reveals a molecular association between Tspan5 and MHC I molecules that is critical for the formation of MHC I nanoclusters and optimal T cell responses to antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Karthik Dhatchinamoorthy, Jeff D. Colbert, Kenneth L. Rock
Summary: Loss of MHC I antigen presentation is common in many cancers, which may impair immune responses and affect the efficacy of immunotherapy. Studies have discussed underlying mechanisms through which some cancers evade immune killing by shutting down the MHC I pathway, and proposed potential strategies to overcome this limitation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Evolutionary Biology
Gemma Palomar, Katarzyna Dudek, Ben Wielstra, Elizabeth L. Jockusch, Michal Vinkler, Jan W. Arntzen, Gentile F. Ficetola, Masatoshi Matsunami, Bruce Waldman, Martin Tesicky, Piotr Zielinski, Wieslaw Babik
Summary: The study found that in urodele amphibians, some APGs are closely linked to MHC I genes, and all APGs show signs of episodic positive selection. However, the detected gene duplications, putative gene losses, and divergent allelic lineages suggest that if there is coevolution between APGs and MHC I, it may be more complex than originally hypothesized.
GENOME BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Ewa Maria Sroka, Mathilde Lavigne, Marika Pla, Chrysoula Daskalogianni, Maria Camila Tovar-Fernandez, Rodrigo Prado Martins, Benedicte Manoury, Guillaume Darrasse-Jeze, Megane Nascimento, Sebastien Apcher, Robin Fahraeus
Summary: This study found that introducing an MHC class I epitope sequence into the intron of the beta-globin gene in mice can generate immune tolerance. Translation initiation within the intron produces peptides for MHC class I immune tolerance, providing an explanation for the tolerance of alternative tissue-specific splicing by the immune system.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Lei Zhan, Junhui Zhang, Jing Zhang, Xiaojing Liu, Suding Zhu, Yuchuan Shi, Yu He, Wenyan Wang, Yijing Wei, Zhenhai Tang, Guo Chen, Bing Wei, Yunxia Cao
Summary: In this study, the researchers found that upregulated autophagy and decreased expression of MHC-I and NLRC5 were associated with endometrial cancer (EC). Inhibition of autophagy was found to suppress MHC-I gene expression. They also discovered that LC3 interacted with NLRC5 to inhibit the NLRC5-mediated MHC-I antigen presentation pathway. These findings suggest that inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy for EC management.
Article
Immunology
Maria Kalomoiri, Chandana Rao Prakash, Sonja Lagstroem, Kai Hauschulz, Ewoud Ewing, Klementy Shchetynsky, Lara Kular, Maria Needhamsen, Maja Jagodic
Summary: The Human Leukocyte Antigen (HLA) locus is associated with various complex diseases, especially autoimmune and inflammatory conditions. The HLA-DR15 haplotype, for example, is a major risk factor for developing Multiple Sclerosis in Caucasians, suggesting its important role in the etiology of this chronic inflammatory disease. Recent studies indicate that the levels of HLA molecule expression, which are epigenetically controlled, also contribute to disease development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Valentina Ferrari, Antonino Lo Cascio, Alessia Melacarne, Nina Tanaskovi, Alessandro M. Mozzarelli, Luca Tiraboschi, Michela Lizier, Marta Salvi, Daniele Braga, Francesca Algieri, Giuseppe Penna, Maria Rescigno
Summary: Recent research has shown that the gut microbiota plays a significant role in the clinical response to immune check-point inhibitors for solid tumors. Metabolites released by bacteria can enhance the expression of HLA class I molecules on cancer cells, leading to increased sensitivity to immune cells and improved tumor clearance.
Article
Immunology
Timothy Connelley, Annalisa Nicastri, Tara Sheldrake, Christina Vrettou, Andressa Fisch, Birkir Reynisson, Soren Buus, Adrian Hill, Ivan Morrison, Morten Nielsen, Nicola Ternette
Summary: This study used immunopeptidomics to study the repertoire of peptides presented by Theileria parva-infected cells. A comprehensive dataset of 74 BoLA-I and 15 BoLA-DR-presented peptides, based on different BoLA genotypes, was generated. The study demonstrated the utility of immunopeptidomics as a method to identify novel T-cell antigens for T. parva.
Article
Biochemistry & Molecular Biology
F. Tudor Ilca, Louise H. Boyle
Summary: The glycosylation status of MHC-I molecules affects their affinity for TAPBPR, with non-glycosylated MHC-I showing stronger interactions and easier peptide exchange compared to glycosylated counterparts. TAPBPR is more resistant to peptide-mediated allosteric release from non-glycosylated MHC-I, indicating the important role of glycans in modulating protein interactions.
MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Yuri Poluektov, Marybeth George, Pirouz Daftarian, Marc C. Delcommenne
Summary: The study focuses on evaluating the binding affinities of SARS-CoV-2 peptides to different MHC alleles using the QuickSwitchTM platform, identifying multiple MHC binders with high promiscuity. These results provide important data for further research on the SARS-CoV-2 virus and its antigenic epitopes.
Article
Multidisciplinary Sciences
Yi Sun, Michael C. Young, Claire H. Woodward, Julia N. Danon, Hau Truong, Sagar Gupta, Trenton J. Winters, Joan Font-Burgada, George M. Burslem, Nikolaos G. Sgourakis
Summary: This study created stable MHC-I molecules capable of accepting low-to moderate-affinity peptides through an engineered disulfide bond bridging conserved epitopes. The effects of the disulfide bond on the conformation of the MHC-I structure were characterized using solution NMR. The structure-guided design provides a universal platform for screening antigenic epitope libraries and studying polyclonal TCR repertoires covering highly polymorphic HLA-I allotypes and oligomorphic nonclassical molecules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Shinji Morisaki, Hideya Onishi, Takafumi Morisaki, Makoto Kubo, Masayo Umebayashi, Hiroto Tanaka, Norihiro Koya, Shinichiro Nakagawa, Kenta Tsujimura, Sachiko Yoshimura, Poh Yin Yew, Kazuma Kiyotani, Yusuke Nakamura, Masafumi Nakamura, Takanari Kitazono, Takashi Morisaki
Summary: Through analysis of four patients, we found that intranodal vaccination with hybrid neoantigen-pulsed DCs successfully induced a strong immune response and provided insight into the mechanisms of action, suggesting future directions in neoantigen vaccine design.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Simon Jasinski-Bergner, Juliane Bluemke, Marcus Bauer, Saskia Luise Skiebe, Ofer Mandelboim, Claudia Wickenhauser, Barbara Seliger
Summary: This study investigates the relationship between human Epstein-Barr virus (EBV) and various cancers, particularly the role of virus-encoded microRNAs (miRs) in the malignant transformation of infected cells and immune evasion. Through the analysis of experimental data and in vitro experiments, the authors identified genes associated with oncogenic properties, immune escape, and anti-tumoral immune responses, and predicted potential candidate EBV-miRs and their target genes. This integrated method helps to deepen our understanding of the functions of EBV-miRs and their eligibility as markers in different EBV-associated tissues.
Article
Oncology
Karthikeyan Subbarayan, Chiara Massa, Sandra Leisz, Andre Steven, Daniel Bethmann, Katharina Biehl, Claudia Wickenhauser, Barbara Seliger
Summary: The extracellular matrix component biglycan (BGN) is reduced in K-RAS-associated malignancies, leading to altered growth properties, reduced immunogenicity, and worse patients' outcome.
Article
Oncology
Chiara Massa, Barbara Seliger
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Miriam Moller, Steffi Turzer, Georgi Ganchev, Andreas Wienke, Wolfgang Schutte, Barbara Seliger, Dagmar Riemann
Summary: The study aimed to identify blood cell parameters correlating with the survival of non-small cell lung cancer patients undergoing immune checkpoint inhibitor therapy combined with chemotherapy. The results suggest that specific blood cell parameters, such as neutrophil-to-lymphocyte ratio, special types of monocytes, and dendritic cell numbers, may serve as predictive biomarkers for cancer patients' survival.
Article
Oncology
Christoforos K. Vaxevanis, Michael Friedrich, Sandy Uta Tretbar, Diana Handke, Yuan Wang, Juliane Bluemke, Reinhard Dummer, Chiara Massa, Barbara Seliger
Summary: This study revealed a novel mechanism in which miRNAs targeting the coding sequence of immune checkpoint genes are functional and have prognostic relevance. It also has the potential for the development of novel miRNA-based therapies.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Barbara Seliger, Simon Jasinski-Bergner, Chiara Massa, Anja Mueller, Katharina Biehl, Bo Yang, Michael Bachmann, Danny Jonigk, Philip Eichhorn, Arndt Hartmann, Claudia Wickenhauser, Marcus Bauer
Summary: The expression of non-classical human leukocyte antigen (HLA)-G is elevated in lung tissues of SARS-CoV-2 infected patients, correlating with immune cell infiltration, altered CD8(+) cell numbers, and changes in lung epithelial cell function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Christoforos K. K. Vaxevanis, Marcus Bauer, Karthikeyan Subbarayan, Michael Friedrich, Chiara Massa, Katharina Biehl, Haifa Kathrin Al-Ali, Claudia Wickenhauser, Barbara Seliger
Summary: The expression of BGN in MDS and sAML is associated with disease progression and inflammation. BGN is expressed in MDS cell lines and patient bone marrow biopsies, and is involved in regulating inflammasome activity. BGN expression is associated with patient survival in MDS and may serve as a biomarker and potential therapeutic target.
Review
Oncology
Simon Deycmar, Bruno Gomes, Jehad Charo, Maurizio Ceppi, J. Mark Cline
Summary: The complexity of cancer immunotherapy (CIT) requires reliable preclinical models. Non-human primates (NHPs) share similarities with humans and have the potential to bridge the gap between preclinical models and human patients. This review presents the current knowledge of NHP immunology, naturally-occurring cancers in NHPs, and TBM trials investigating CIT.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Dagmar Riemann, Steffi Turzer, Georgi Ganchev, Wolfgang Schuette, Barbara Seliger, Miriam Moeller
Summary: In this study, small cell lung cancer (SCLC) patients were treated with chemotherapy and immune checkpoint inhibitors, and their blood immune cells were analyzed. The study found that certain blood cell parameters, such as neutrophil/lymphocyte ratio, HLA-DRlow monocytes, and NK cell and dendritic cell numbers, were associated with disease progression and poor overall survival. When comparing SCLC with non-SCLC, SCLC had higher metastases frequency, higher neutrophil/lymphocyte ratio, lower dendritic cell frequencies, and lower NK cell numbers. The study suggests that blood immune cell signature could improve prediction of SCLC patient outcomes and provide insights into the characteristics of this tumor entity.
Article
Oncology
Antonino A. A. Pane, Theresa Kordass, Agnes Hotz-Wagenblatt, Elke Dickes, Annette Kopp-Schneider, Rainer Will, Barbara Seliger, Wolfram Osen, Stefan B. B. Eichmueller
Summary: This study identified several miRNA species that can affect the susceptibility of melanoma cells to T cell-mediated killing. These miRNAs may represent attractive candidates for novel therapy approaches against melanoma and other tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Chiara Massa, Yuan Wang, Nico Marr, Barbara Seliger
Summary: Interferons (IFNs) are secreted proteins that provide important information for understanding the immune system and cytokine signaling pathways. They have diverse physiological and pathophysiological activities, including modulation of host responses, tumor surveillance, and immune responses. However, tumor cells often develop resistance to IFNs, and loss-of-function mutations in IFN signaling components are associated with susceptibility to infectious diseases. This review summarizes the function and clinical relevance of IFNs, particularly their role in tumor immune evasion and pathogen clearance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
WeiQing Venus So, David Dejardin, Eva Rossmann, Jehad Charo
Summary: In this study, we found that standard blood analytes had prognostic utility, while tumor PD-L1 and tumor mutational burden (TMB) could predict the response of non-small cell lung cancer patients to immune checkpoint inhibitors. Patients with high TMB and high PD-L1 expression showed durable response to immune checkpoint inhibitors. Non-squamous histology, smoking history, and prior chemotherapy enhanced the predictive effect of PD-L1.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Medicine, Research & Experimental
Helene Schaefer, Karthikeyan Subbarayan, Chiara Massa, Christoforos Vaxevanis, Anja Mueller, Barbara Seliger
Summary: Using bioinformatics analysis, we found that the expression of ECM protein PRELP is reduced in cutaneous melanoma and is associated with decreased patient survival. High PRELP expression is correlated with low expression of MHC class I antigen processing machinery (APM) and interferon (IFN)-γ pathway, as well as increased expression of TFGB1 and TGFBR1. Transfection of PRELP restores MHC class I surface expression and reduces cell proliferation, migration, and invasion in melanoma cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Miriam Moeller, Wolfgang Schuette, Steffi Turzer, Barbara Seliger, Dagmar Riemann
Summary: This pilot study conducted immune monitoring in advanced non-small cell lung cancer (NSCLC) patients and found that low neutrophil/lymphocyte ratio (NLR), low percentage of suppressive HLA-DRlow monocytes, and clearly detectable numbers of slan+ non-classical monocytes and dendritic cells might be predictive markers for therapy responses and treatment outcomes.
Article
Biochemistry & Molecular Biology
Matthias Bache, Frauke Kadler, Olivia Struck, Daniel Medenwald, Christian Ostheimer, Antje Guettler, Jacqueline Kessler, Matthias Kappler, Anne Riemann, Oliver Thews, Barbara Seliger, Dirk Vordermark
Summary: The concentration of miR-16, miR-29a, and miR-144 in the plasma of NSCLC patients undergoing radiotherapy was evaluated, and their impact on patients' prognosis was assessed. The results showed that the plasma levels of miR-16, miR-29a, and miR-144 had prognostic value in NSCLC patients, while the level of miR-150 did not predict prognosis. Patients with low levels of these three miRs in their plasma at the end of radiotherapy had the worst prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)