Article
Multidisciplinary Sciences
Erietta Stelekati, Zhangying Cai, Sasikanth Manne, Zeyu Chen, Jean-Christophe Beltra, Lance Alec Buchness, Xuebing Leng, Svetlana Ristin, Kito Nzingha, Viktoriya Ekshyyan, Christina Niavi, Mohamed S. Abdel-Hakeem, Mohammed-Alkhatim Ali, Sydney Drury, Chi Wai Lau, Zhen Gao, Yuguang Ban, Simon K. Zhou, K. Mark Ansel, Makoto Kurachi, Martha S. Jordan, Alejandro V. Villarino, Shin Foong Ngiow, E. John Wherry
Summary: This study identifies miR-29a as a key regulator of exhausted CD8 T cells (TEX) during chronic viral infection. It shows that miR-29a improves CD8 T cell responses, inhibits exhaustion-driving transcriptional pathways, and regulates ribosomal biogenesis. As a result, miR-29a promotes a memory-like CD8 T cell differentiation state during chronic infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Huarong Zhou, Bei Jia, Charyguly Annageldiyev, Kentaro Minagawa, Chenchen Zhao, Shin Mineishi, W. Christopher Ehmann, Seema G. Naik, Joseph Cioccio, Baldeep Wirk, Natthapol Songdej, Kevin L. Rakszawski, Myles S. Nickolich, Jianzhen Shen, Hong Zheng
Summary: Acute myeloid leukemia (AML) is a devastating blood cancer with a need for new effective treatments. Immunotherapy targeting T cell exhaustion by blocking inhibitory pathways, such as PD-1, is promising but has been disappointing in clinical studies with AML patients. CD26(low)PD-1(+) CD8 T cells have been found to be associated with AML progression and exhaustion, suggesting a prognostic and predictive value of CD26 in AML.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Sara Alavi, Abdullah Al Emran, Hsin-Yi Tseng, Jessamy C. Tiffen, Helen Marie McGuire, Peter Hersey
Summary: This study explores the role of nicotinamide in preventing and reversing T cell exhaustion, which has important implications for immunotherapy against cancers and viral infections. Nicotinamide supplementation was found to prevent the development of inhibitory receptors in T cells and promote the differentiation of T cells to effector states, suggesting a potential therapeutic strategy for enhancing immune responses.
Article
Immunology
Jiaqi Hu, Chongyin Han, Jiayuan Zhong, Huisheng Liu, Rui Liu, Wei Luo, Pei Chen, Fei Ling
Summary: The study identified CCT6A as a biomarker for pre-exhausted T-cell subpopulation in CRC, while TUBA1B acts as core genes contributing to CD8(+) T cell exhaustion. Additionally, cellular communication between terminally differentiated exhausted T cells and pre-exhausted T cells contributes to exhaustion.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ling Li, Manzhi Zhao, Caoimhe H. Kiernan, Melisa D. Castro Eiro, Marjan van Meurs, Inge Brouwers-Haspels, Merel E. P. Wilmsen, Dwin G. B. Grashof, Harmen J. G. van de Werken, Rudi W. Hendriks, Yvonne M. Mueller, Peter D. Katsikis
Summary: This study demonstrates that ibrutinib directly ameliorates CTL exhaustion by reducing inhibitory receptor expression, enhancing cytokine production, and modulating the transcription factors TOX and TCF1. Additionally, the effect of ibrutinib is independent of BTK expression, suggesting the involvement of other targets.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Gaia Montacchiesi, Luigia Pace
Summary: After antigen recognition, CD8(+) T lymphocytes differentiate into different subsets with distinct phenotypes, functions, and migration properties. Transcription factors and chromatin structure changes drive the functional differentiation and phenotypic diversity of these T cell subsets, which has implications for new immunotherapy protocols and vaccination strategies. Understanding the contribution of chromatin architecture and transcription factor activity in guiding CD8(+) T cell subset commitment is important for T cell plasticity, stability, and memory in infection and cancer.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Cell Biology
Stefan Naulaerts, Angeliki Datsi, Daniel M. Borras, Asier Antoranz Martinez, Julie Messiaen, Isaure Vanmeerbeek, Jenny Sprooten, Raquel S. Laureano, Jannes Govaerts, Dena Panovska, Marleen Derweduwe, Michael C. Sabel, Marion Rapp, Weiming Ni, Sean Mackay, Yannick Van Herck, Lendert Gelens, Tom Venken, Sanket More, Oliver Bechter, Gabriele Bergers, Adrian Liston, Steven De Vleeschouwer, Benoit J. Van Den Eynde, Diether Lambrechts, Michiel Verfaillie, Francesca Bosisio, Sabine Tejpar, Jannie Borst, Rudiger V. Sorg, Frederik De Smet, Abhishek D. Garg
Summary: Through multiomics analysis of CD8+ T cell features in multiple patient cohorts and tumor types, we have identified different hypofunctional states of tumor-associated CD8+ T cells, including exhausted CD8+ T cells in supportive tumor niches and hypofunctional CD8+ T cells in nonsupportive niches. These two types of hypofunctional states exhibit distinct characteristics, such as different T cell receptor repertoires and immunopeptidomes. Furthermore, dysfunctional CD4+:CD8+ T cell interactions and a wound healing-like chemokine profile were observed in glioblastoma. Immuno-oncology clinical trials showed that anti-programmed cell death protein 1 (PD-1) immunotherapy exacerbated the tolerogenic disparities in glioblastoma, while dendritic cell (DC) vaccines partially corrected them. Recipients of DC vaccines for glioblastoma demonstrated evidence of antigen-specific immunity.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Wai Ki Wong, Bohan Yin, Ching Ying Katherine Lam, Yingying Huang, Jiaxiang Yan, Zhiwu Tan, Siu Hong Dexter Wong
Summary: This article discusses the importance of epigenetic regulation of T-cell function in cancer immunotherapy and how to restore their function by modulating the epigenetic switches of T-cells, providing new therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Joseph S. Dolina, Natalija Van Braeckel-Budimir, Graham D. Thomas, Shahram Salek-Ardakani
Summary: Recent research has revealed the heterogeneity within the exhausted CD8(+) T cell lineage, which consists of multiple interconnected subpopulations with distinct characteristics and locations. This understanding calls for a re-focusing of cancer immunotherapies on targeting the driver mechanisms underlying CD8(+) T(ex) development to stabilize functional subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Maike Hofmann, Catrin Tauber, Nina Hensel, Robert Thimme
Summary: CD8(+) T cell responses play a crucial role in chronic HCV infection and HCC, strong virus-specific CD8(+) T cell responses contribute to virus clearance while failure leads to chronic infection development. Tumor-associated and tumor-specific CD8(+) T cells are considered potential targets for immunotherapeutic strategies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Nadia Bannoud, Tomas Dalotto-Moreno, Lucia Kindgard, Pablo A. Garcia, Ada G. Blidner, Karina V. Marino, Gabriel A. Rabinovich, Diego O. Croci
Summary: This study highlights the reciprocal regulation between hypoxia, angiogenesis, and immunosuppression in tumor progression and anti-tumor therapies. The findings suggest a rational basis for optimizing synergistic combinations of antiangiogenic and immunotherapeutic strategies to enhance treatment efficacy.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Wooseok Seo, Chandsultana Jerin, Hiroyoshi Nishikawa
Summary: Exhausted CD8(+) T cells may be deliberately generated and maintained to provide mild immune responses against chronic infection or cancer, which can be safer over the long term compared to strong immune responses. A specific population of exhausted CD8(+) T cells that behaves like self-renewing stem cells has been identified, suggesting they can be considered progenitors of exhausted CD8(+) T cells. Studies have revealed the regulatory network governing the generation and propagation of exhausted CD8(+) T cells, shedding light on the developmental stages that lead to this subtle but effective immune response.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Review
Immunology
Alessio Bevilacqua, Zhiyu Li, Ping-Chih Ho
Summary: This article reviews how metabolism affects the differentiation and function of CD8(+) T cells, as well as the principal metabolic dysregulation that leads to the exhausted phenotype. The article also summarizes recent strategies to reprogram impaired metabolic pathways to promote CD8(+) T cell effector function and survival.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Jia-Tong Ding, Kang-Ping Yang, Hao-Nan Zhou, Ying-Feng Huang, Hui Li, Zhen Zong
Summary: CD8(+) T cells, a key component of the tumor immune system, enter a hyporeactive state in chronic inflammation, and understanding the mechanisms of T cell exhaustion is crucial for immunotherapeutic development. Transcription factors and epigenetic regulation may play a role in the heterogeneity and kinetics of CD8(+) T cell exhaustion, providing potential targets for immunotherapy. Gastrointestinal cancers show better anti-tumor T cell composition, indicating promising prospects for precision-targeted immunotherapy. This study focuses on the mechanisms and clinical applications of CD8(+) T cell exhaustion in gastrointestinal cancer, providing insights for future immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Janine Kemming, Swantje Gundlach, Marcus Panning, Daniela Huzly, Jiabin Huang, Marc Luetgehetmann, Sven Pischke, Julian Schulze Zur Wiesch, Florian Emmerich, Sian Llewellyn-Lacey, David A. Price, Yakup Tanriver, Klaus Warnatz, Tobias Boettler, Robert Thimme, Maike Hofmann, Nicole Fischer, Christoph Neumann-Haefelin
Summary: Chronic HEV infection is associated with exhaustion of HEV-specific CD8+ T cells, indicating that T-cell failure is driven by persistent antigen recognition in severely immunosuppressed hosts. Functional reinvigoration of virus-specific T cells is at least partially possible when the antigen is cleared. Viral escape in a minority of patients also contributes to the failure of HEV-specific CD8+ T cells.
JOURNAL OF HEPATOLOGY
(2022)
Editorial Material
Oncology
Xiao-Jie Lu
Editorial Material
Oncology
Jin-Yu Sun, Xiao-Jie Lu
Editorial Material
Genetics & Heredity
Xiaoling Weng, Xiao-Jie Lu
Article
Cell Biology
Jianfei Tu, Weiqian Chen, Liyun Zheng, Shiji Fang, Dengke Zhang, Chunli Kong, Yang Yang, Rongfang Qiu, Zhongwei Zhao, Chenying Lu, Xiaojie Lu, Jiansong Ji
Summary: The study revealed that circ_0021205 was up-regulated in CCA and positively correlated with tumor size and TNM stage. It promoted the proliferation, migration, and invasion of CCA cells by sponging miR-204-5p and regulating the expression of RAB22A, serving as a potential diagnostic biomarker or therapeutic target for CCA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Wenjie Zhang, Guangyan Zhangyuan, Fei Wang, Kangpeng Jin, Haiyuan Shen, Liansheng Zhang, Xiang Yuan, Jincheng Wang, Haitian Zhang, Weiwei Yu, Ruyi Huang, Xiaoliang Xu, Yin Yin, Guisheng Zhong, Anning Lin, Beicheng Sun
Summary: Chronic inflammation in hepatocellular carcinoma (HCC) is influenced by the zinc finger transcription factor Miz1, which restricts hepatocyte-driven inflammation through sequestration of the oncoprotein metadherin (MTDH) and prevention of NF-kappa B activation. Miz1 acts as a tumor suppressor by preventing a subset of hepatocytes from promoting inflammation in HCC, leading to disease recurrence and poor prognosis in patients.
Review
Immunology
Jin-Yu Sun, Rui Wu, Jiang Xu, Hui-Ying Xue, Xiao-Jie Lu, Jiansong Ji
Summary: The immune system plays a crucial role in recognizing and attacking non-self antigens, leading to immunity against infection. However, it also causes immune rejection during organ transplantation. Understanding the mechanisms of maternal-fetal immune tolerance can potentially improve transplantation outcomes by balancing immune tolerance and infection defense. Studies exploring the interconnection between immune tolerance in pregnancy and organ transplantation highlight the impact of pregnancy alloimmunization on transplant success.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Cell Biology
Xiaoling Weng, Xiao-Jie Lu
CELLULAR SIGNALLING
(2021)
Article
Cell Biology
Xiaochen Wang, Jianchu Wang, Haiyuan Shen, Zongjiang Luo, Xiaojie Lu
Summary: This study found that TPX2 regulates the antitumor effect of CD8 + T cells in hepatocellular carcinoma (HCC) by modulating CXCR5. Overexpression of TPX2 enhances the anticancer function of CD8 + T cells and shows synergistic effects with anti-PD-1 therapy.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Naoto Fujiwara, Naoto Kubota, Emilie Crouchet, Bhuvaneswari Koneru, Cesia A. Marquez, Arun K. Jajoriya, Gayatri Panda, Tongqi Qian, Shijia Zhu, Nicolas Goossens, Xiaochen Wang, Shuang Liang, Zhenyu Zhong, Sara Lewis, Bachir Taouli, Myron E. Schwartz, Maria Isabel Fiel, Amit G. Singal, Jorge A. Marrero, Austin J. Fobar, Neehar D. Parikh, Indu Raman, Quan-Zhen Li, Masataka Taguri, Atsushi Ono, Hiroshi Aikata, Takashi Nakahara, Hayato Nakagawa, Yuki Matsushita, Ryosuke Tateishi, Kazuhiko Koike, Masahiro Kobayashi, Takaaki Higashi, Shigeki Nakagawa, Yo-ichi Yamashita, Toru Beppu, Hideo Baba, Hiromitsu Kumada, Kazuaki Chayama, Thomas F. Baumert, Yujin Hoshida
Summary: This study analyzed multiple cohorts of NAFLD patients globally to define and validate signatures predictive of long-term HCC risk in NAFLD patients. These signatures can accurately predict the risk of developing HCC in patients and provide assistance for clinical treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Liangliang Zhou, Haiyuan Shen, Xiaofeng Li, Hua Wang
Summary: This review discusses the role of innate immune cells and their endoplasmic reticulum stress in the occurrence of NAFLD and the progression of cirrhosis. Complex immune responses and ER stress play a critical role in triggering and amplifying hepatic inflammation and fibrosis, revealing the underlying mechanisms of NAFLD/NASH.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Oncology
Zhangya Pu, Zhigang Ren, Qiuran Xu, Xiaochen Wang, Jian Chen, Jiang Chen
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Xiaochen Wang, Qifeng He, Chuanli Zhou, Yueyuan Xu, Danhui Liu, Naoto Fujiwara, Naoto Kubota, Arielle Click, Polly Henderson, Janiece Vancil, Cesia Ammi Marquez, Ganesh Gunasekaran, Myron E. Schwartz, Parissa Tabrizian, Umut Sarpel, Maria Isabel Fiel, Yarui Diao, Beicheng Sun, Yujin Hoshida, Shuang Liang, Zhenyu Zhong
Summary: Obesity-induced chronic liver inflammation, a characteristic of NASH, is sustained in the liver through the macrophage phagocytic receptor TREM2. However, prolonged hypernutrition leads to the shedding of TREM2, resulting in the accumulation of dying hepatocytes and augmenting proinflammatory cytokine production. This vicious cycle drives the transition from simple steatosis to NASH, highlighting impaired macrophage efferocytosis as a key pathogenic event.
Review
Gastroenterology & Hepatology
Hejiao Zhang, Haiyuan Shen, Liangliang Zhou, Linxi Xie, Derun Kong, Hua Wang
Summary: Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes that recognize riboflavin metabolites. Their role in human diseases, particularly in gastric, esophageal, intestinal, and hepatobiliary diseases, is discussed in this review. Understanding MAIT cells better will lead to more effective therapeutic approaches for digestive diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)