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.
Review
Biochemistry & Molecular Biology
Akhil Shukla, Maryse Cloutier, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The immune system constantly monitors and eliminates cancerous cells, with CD8(+) cytotoxic T lymphocytes playing a key role in tumor cell killing. Cancer cells evade immune surveillance by downregulating MHC-I and key proteins of the antigen processing and presentation machinery. NLRC5 has been identified as the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are common causes of MHC-I defects in cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sayuri Yoshihama, Steven X. Cho, Jason Yeung, Xuedong Pan, Gregory Lizee, Kranti Konganti, Valen E. Johnson, Koichi S. Kobayashi
Summary: The expression of NLRC5 and MHC class I-related genes is crucial for the effective response of melanoma patients to anti-CTLA-4 and anti-PD1 checkpoint blockade immunotherapy, serving as potential predictive biomarkers for prognosis and treatment response.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Kishore Nagasubramanian, Shanker Jha, Anuranjan Singh Rathore, Krishnakant Gupta
Summary: The study aimed to identify potential modulators for CIITA-I by predicting its structure, docking with small molecule databases, and conducting molecular simulations. Two potential modulators, ZINC5154833 and F5254-0161, were identified based on their interaction strength with CIITA-I.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Yusuke Kasuga, Ryota Ouda, Masashi Watanabe, Xin Sun, Miki Kimura, Shigetsugu Hatakeyama, Koichi S. Kobayashi
Summary: Major histocompatibility complex (MHC) class I and II molecules are critical for adaptive immunity. The protein FBXO11 has been identified as an E3 ligase that regulates CIITA protein level through ubiquitination-mediated degradation, thus determining the level of MHC-II.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Chrissie E. B. Ong, Yuanyuan Cheng, Hannah V. Siddle, A. Bruce Lyons, Gregory M. Woods, Andrew S. Flies
Summary: MHC-I and MHC-II molecules play critical roles in antigen presentation and T cell immunity. Two transmissible devil facial tumours (DFT1 and DFT2) exploit the MHC-I pathway to overcome immune and allogeneic barriers. This study reveals that overexpression of NLRC5 regulates the MHC-I pathway and raises interest in the expression of MHC-II in tumor cells. This finding has important implications for immunotherapy and cancer vaccine research.
Review
Biochemistry & Molecular Biology
Jorge Alfonso Leon Machado, Viktor Steimle
Summary: CIITA is the master regulator of MHC class II gene expression, functioning as a non-DNA-binding activator through interactions with the MHC enhanceosome complex. In addition to its role in MHC-II gene regulation, CIITA also plays important roles in cancer, viral restriction, and inhibition of virus replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Fabrizio Celesti, Andrea Gatta, Mariam Shallak, Anna Maria Chiaravalli, Michele Cerati, Fausto Sessa, Roberto S. Accolla, Greta Forlani
Summary: In an animal experimental system, vaccination with glioblastoma GL261 cells expressing CIITA showed successful protection against glioblastoma growth. The activation of MHC class II through CIITA led to rapid infiltration of CD4+ and CD8+ T cells, resulting in the rejection or retardation of tumor growth. This approach demonstrates the potential application of novel immunotherapeutic strategies in the clinical setting.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Steven X. Cho, Saptha Vijayan, Ji-Seung Yoo, Toshiyuki Watanabe, Ryota Ouda, Ning An, Koichi S. Kobayashi
Summary: The presentation of antigenic peptides by MHC class I and class II molecules is crucial for activating the adaptive immune system, with CIITA and NLRC5 serving as the major transcriptional activators of MHC class II and class I gene expression. Recent advances in understanding the role of NLRC5 in infectious diseases and cancer have shed light on its biological significance and mechanism in MHC class I expression.
Article
Biochemistry & Molecular Biology
Madanraj Appiya Santharam, Akhil Shukla, Dominique Levesque, Thomas A. Kufer, Francois-Michel Boisvert, Sheela Ramanathan, Subburaj Ilangumaran
Summary: Aggressive tumors avoid immune attack by suppressing MHC-I expression. NLRC5 is a transcriptional activator of MHC-I, and defects in NLRC5 result in MHC-I defects. Restoring NLRC5 expression in poorly immunogenic B16 melanoma cells induces MHC-I and antitumor immunity, suggesting the potential use of NLRC5 for tumor immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Xiang Liu, Lingdan Yin, Mei Xue, Jianfei Chen, Liang Li, Fang Fu, Li Feng, Pinghuang Liu
Summary: It was found that porcine deltacoronavirus (PDCoV) infection upregulated the expression of porcine MHC-I molecules and associated genes, but not MHC-II molecules. This upregulation was mediated through the enhancement of NLRC5 expression by PDCoV, which was regulated by RIG-I-initiated type I interferon signaling pathway and IRF1. These findings provide insights into the manipulation of MHC molecules by PDCoV and may have implications for the development of therapies and vaccines against PDCoV.
JOURNAL OF VIROLOGY
(2022)
Review
Immunology
Magdalena Godkowicz, Magdalena Druszczynska
Summary: This review discusses the role of NOD1, NOD2, and NLRC5 receptors in regulating antiviral and antimycobacterial immune responses and their potential implications, providing insight into their molecular mechanisms.
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.
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)
Review
Biochemistry & Molecular Biology
Greta Forlani, Mariam Shallak, Andrea Gatta, Amruth K. B. Shaik, Roberto S. Accolla
Summary: This review focuses on the NLR family and its key member, CIITA, which plays important roles in regulating immune system homeostasis, inflammation, and cell death. CIITA is a unique example of a regulator of both intrinsic and adaptive immunity, and recent studies have revealed its dual role in protecting against human retroviruses and inducing expression of MHC-II molecules in cancer cells.
BIOMEDICAL JOURNAL
(2023)
Article
Immunology
Judith Agudo, Eun Sook Park, Samuel A. Rose, Eziwoma Alibo, Robert Sweeney, Maxime Dhainaut, Koichi S. Kobayashi, Ravi Sachidanandam, Alessia Baccarini, Miriam Merad, Brian D. Brown
Article
Food Science & Technology
Tingting Chen, Anna B. Liu, Shili Sun, Nadim J. Ajami, Matthew C. Ross, Hong Wang, Le Zhang, Kenneth Reuhl, Koichi Kobayashi, Janet C. Onishi, Liping Zhao, Chung S. Yang
MOLECULAR NUTRITION & FOOD RESEARCH
(2019)
Review
Immunology
Steven X. Cho, Saptha Vijayan, Ji-Seung Yoo, Toshiyuki Watanabe, Ryota Ouda, Ning An, Koichi S. Kobayashi
Summary: The presentation of antigenic peptides by MHC class I and class II molecules is crucial for activating the adaptive immune system, with CIITA and NLRC5 serving as the major transcriptional activators of MHC class II and class I gene expression. Recent advances in understanding the role of NLRC5 in infectious diseases and cancer have shed light on its biological significance and mechanism in MHC class I expression.
Article
Immunology
Mohamed Benhammadi, Justine Mathe, Maude Dumont-Lagace, Koichi S. Kobayashi, Louis Gaboury, Sylvie Brochu, Claude Perreault
JOURNAL OF IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Sayuri Yoshihama, Steven X. Cho, Jason Yeung, Xuedong Pan, Gregory Lizee, Kranti Konganti, Valen E. Johnson, Koichi S. Kobayashi
Summary: The expression of NLRC5 and MHC class I-related genes is crucial for the effective response of melanoma patients to anti-CTLA-4 and anti-PD1 checkpoint blockade immunotherapy, serving as potential predictive biomarkers for prognosis and treatment response.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Justine Mathe, Mohamed Benhammadi, Koichi S. Kobayashi, Sylvie Brochu, Claude Perreault
Summary: Lung infections are a major cause of death worldwide. Inhalation of the TLR4 ligand LPS is found to significantly upregulate MHC I expression on mouse lung epithelial cells. This upregulation is dependent on the production of three IFN families but limited in AT1 cells due to gene expression restrictions. Genes involved in cytokine and chemokine production are selectively induced in AT1 cells, while specific gene subsets are downregulated in AT2 or bronchiolar cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Ji-Seung Yoo, Michihito Sasaki, Steven X. Cho, Yusuke Kasuga, Baohui Zhu, Ryota Ouda, Yasuko Orba, Paul de Figueiredo, Hirofumi Sawa, Koichi S. Kobayashi
Summary: The authors show that SARS-CoV-2 targets key transcriptional regulators of the MHC class I pathway to hinder antigen presentation, revealing an immune evasion mechanism that suppresses host immune response.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Ying-Shiuan Chen, Jia Li, Sultan Neja, Sabeeta Kapoor, Jorge Enrique Tovar Perez, Chakrapani Tripathi, Rani Menon, Arul Jayaraman, Kyongbum Lee, Wan Mohaiza Dashwood, Shan Wang, Ke Zhang, Koichi Kobayashi, Praveen Rajendran, Roderick Dashwood
Summary: This study reveals the link between spinach-derived linoleate and butanoate metabolites and anticancer effects in a genetic model of colorectal cancer. Mechanistic studies demonstrate that these metabolites target HDAC activity and the IFN-gamma signaling axis. The clinical translation of these findings could have significant implications for delaying surgical interventions and drug therapies in at-risk patients.
Article
Multidisciplinary Sciences
Yusuke Kasuga, Ryota Ouda, Masashi Watanabe, Xin Sun, Miki Kimura, Shigetsugu Hatakeyama, Koichi S. Kobayashi
Summary: Major histocompatibility complex (MHC) class I and II molecules are critical for adaptive immunity. The protein FBXO11 has been identified as an E3 ligase that regulates CIITA protein level through ubiquitination-mediated degradation, thus determining the level of MHC-II.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Pharmacology & Pharmacy
Baohui Zhu, Ryota Ouda, Paul de Figueiredo, Koichi S. Kobayashi
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Oncology
Fengguang Guo, Jugal K. Das, Koichi S. Kobayashi, Qing-Ming Qin, Thomas A. Ficht, Robert C. Alaniz, Jianxun Song, Paul De Figueiredo
Summary: This study demonstrates that live attenuated bacterial treatment can improve antitumor immunity by remodeling the tumor microenvironment, overcoming cancer resistance to chimeric antigen receptor T-cell therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Immunology
Saptha Vijayan, Torsten B. Meissner, Kyoung-Hee Lee, Yuen-Joyce Liu, Isaac Downs, Tabasum Sidiq, Chi Zhang, Peter J. van den Elsen, Koichi S. Kobayashi
JOURNAL OF IMMUNOLOGY
(2019)