Review
Biochemistry & Molecular Biology
Elena Shklovskaya, Helen Rizos
Summary: It is well acknowledged that the immune system plays a role in controlling tumor growth, but tumors can escape immune surveillance through mechanisms like downregulation or loss of MHC-I molecules. This review examines the dysregulation of MHC-I expression in cancer, the nature of MHC-I-bound antigenic peptides, and discusses therapeutic strategies to address MHC-I deficiency in solid tumors with a focus on NK cells and CD4 T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Maciej J. J. Lazarczyk, Brett A. A. Eyford, Merina Varghese, Hitesh Arora, Lonna Munro, Tahia Warda, Cheryl G. G. Pfeifer, Allison Sowa, Daniel R. R. Dickstein, Timothy Rumbell, Wilfred A. A. Jefferies, Dara L. L. Dickstein
Summary: MHC-I proteins are expressed in neurons and regulate synaptic plasticity, but their mechanisms in the CNS are still unknown. This study provides the first structural analysis of a MHC-I protein, revealing its underlying mechanisms in the brain. The Y321F mutation of MHC-I affects spine density and synaptic structure in the hippocampus, without impacting neuronal complexity, and mimics the phenotype of MHC-I knock-out animals, suggesting a crucial role of reverse, outside-in signaling events in regulating synaptic plasticity.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Patrick C. Lee, Susan Klaeger, Phuong M. Le, Keegan Korthauer, Jingwei Cheng, Varsha Ananthapadmanabhan, Thomas C. Frost, Jonathan D. Stevens, Alan Y. L. Wong, J. Bryan Iorgulescu, Anna Y. Tarren, Vipheaviny A. Chea, Isabel P. Carulli, Camilla K. Lemvigh, Christina B. Pedersen, Ashley K. Gartin, Siranush Sarkizova, Kyle T. Wright, Letitia W. Li, Jason Nomburg, Shuqiang Li, Teddy Huang, Xiaoxi Liu, Lucas Pomerance, Laura M. Doherty, Annie M. Apffel, Luke J. Wallace, Suzanna Rachimi, Kristen D. Felt, Jacquelyn O. Wolff, Elizabeth Witten, Wandi Zhang, Donna Neuberg, William J. Lane, Guanglan Zhang, Lars R. Olsen, Manisha Thakuria, Scott J. Rodig, Karl R. Clauser, Gabriel J. Starrett, John G. Doench, Sara J. Buhrlage, Steven A. Carr, James A. DeCaprio, Catherine J. Wu, Derin B. Keskin
Summary: This study reveals transcriptional suppression of HLA-I antigen presentation in Merkel cell carcinoma and identifies MYCL, PRC1.1, and USP7 as regulators in this process.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biology
Tamara S. Rodems, Erika Henninger, Charlotte N. Stahlfeld, Cole S. Gilsdorf, Kristin N. Carlson, Madison R. Kircher, Anupama Singh, Timothy E. G. Krueger, David J. Beebe, David F. Jarrard, Douglas G. McNeel, Michael C. Haffner, Joshua M. Lang
Summary: Loss of HLA-I gene expression in prostate cancer is associated with repressive chromatin states, which can be reversed by pharmacological inhibition of DNMT and HDAC, leading to increased activation of CD8+ T-cells. HLA-I expression is epigenetically regulated by DNA methylation and chromatin modifications.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Zhiran Zou, Xiao Long, Qian Zhao, Yandong Zheng, Moshi Song, Shuai Ma, Yaobin Jing, Si Wang, Yifang He, Concepcion Rodriguez Esteban, Nanze Yu, Jiuzuo Huang, Piu Chan, Ting Chen, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Guang-Hui Liu
Summary: Single-cell RNA sequencing of human eyelid skin revealed progressive accumulation of photoaging-related changes and increased chronic inflammation with age. Transcriptional factors involved in the developmental process showed early-onset decline during aging. Inhibition of key transcription factors HES1 and KLF6 compromised cell proliferation, increased inflammation, and accelerated cellular senescence during aging.
DEVELOPMENTAL CELL
(2021)
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
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
Biochemical Research Methods
Max Hoek, Laura C. Demmers, Wei Wu, Albert J. R. Heck
Summary: The study analyzed in depth the N-glycosylation features of HLA class I molecules, finding that HLA-A alpha-chains have distinct glycosylation patterns compared to HLA-B, HLA-C, and HLA-F. The cellular distribution of HLA molecules varies based on their glycosylation features, with HLA-B predominantly found at the plasma membrane, and HLA-C and HLA-F mainly located in the endoplasmic reticulum and Golgi membrane. The findings highlight the importance of considering allotype-specific cellular distribution when analyzing peptide antigen presentation in immunopeptidomics.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Dermatology
Romana Sinova, Vojtech Pavlik, Matej Simek, Martin Cepa, Martin Ondrej, Kristina Nesporova, Vladimir Velebny
Summary: Exposure to the sun can lead to UV-induced skin damage, and this study investigated the changes in hyaluronan (HA) metabolism in the skin after UV exposure. The results showed that UV irradiation increased the amount of HA in the skin and altered the expression of related genes and proteins. These findings suggest that UV exposure affects HA metabolism in the skin and that this response may be modulated by the underlying dermis.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Shotaro Nakajima, Kosaku Mimura, Takuro Matsumoto, Aung Kyi Thar Min, Misato Ito, Hiroshi Nakano, Prajwal Neupane, Yasuyuki Kanke, Hirokazu Okayama, Motonobu Saito, Tomoyuki Momma, Yohei Watanabe, Hiroyuki Hanayama, Suguru Hayase, Zenichiro Saze, Koji Kono
Summary: Trastuzumab deruxtecan (T-DXd) exhibits an excellent anti-tumor effect through increasing the number of tumor-infiltrating CD8(+) T cells and enhancing major-histocompatibility-complex class I expression in a mouse model. However, its impact on anti-tumor immune responses in human cancers remains largely unknown.
SCIENTIFIC REPORTS
(2021)
Article
Biochemical Research Methods
Raphael Trevizani, Zhen Yan, Jason A. Greenbaum, Alessandro Sette, Morten Nielsen, Bjoern Peters
Summary: An approach to assess the reliability of different metrics for evaluating the performance of MHC class I binding predictors was developed. The study found that using percentile-ranked results improved the stability of the ranks and identified the top-performing tools in the benchmark.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Andong Zhao, Hua Qin, Mengli Sun, Mao Tang, Jinyu Mei, Kui Ma, Xiaobing Fu
Summary: Intestinal goblet cells, derived from human epidermal stem cells using small molecular inhibitors and growth factors, can model mucus-microbe interaction and aid in the repair of colitis, demonstrating potential for investigating gut health and developing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Yuki Uchihara, Tiara Bunga Mayang Permata, Hiro Sato, Reika Kawabata-Iwakawa, Sayako Katada, Wenchao Gu, Sangeeta Kakoti, Motohiro Yamauchi, Reona Kato, Soehartati Gondhowiardjo, Naoki Hosen, Takaaki Yasuhara, Atsushi Shibata
Summary: This study reveals that DNA damage signaling can produce immunogenic antigens by utilizing the machinery of PRT/NMD. DNA damage upregulates HLA class I antigen presentation, and antigen production is essential. Additionally, the pioneer translation factor CBP20, which initiates nonsense-mediated mRNA decay, plays a critical role in antigen production.
Article
Engineering, Biomedical
Lidan Zhang, Ying Cen, Qiaorong Huang, Huifang Li, Xianming Mo, Wentong Meng, Junjie Chen
Summary: This study utilized flow cytometry and automated analysis methods to reveal the heterogeneity of epidermis in human skin, showing distribution differences between different body sites, which provides important insights for better understanding skin homeostasis and wound healing.
BIOMEDICAL ENGINEERING ONLINE
(2021)
Article
Biochemistry & Molecular Biology
Nina Geng, Tuo Hu, Chunbo He
Summary: Immune checkpoint blockade therapies show durable responses in a subset of colorectal cancer patients, but the majority do not respond. Our study suggests that DDX60 may regulate MHC-I expression in colorectal cancer, and targeting DDX60 could potentially improve the efficacy of immunotherapy.
