☆ 4.8 Editorial Material

Back to the Future: Effector Fate during T Cell Exhaustion

IMMUNITY (2019)

期刊

IMMUNITY

卷 51, 期 6, 页码 970-972

出版社

CELL PRESS

DOI: 10.1016/j.immuni.2019.11.007

关键词

-

类别

Immunology

向作者/读者索取更多资源

Protocol

Reagent

摘要

Exhausted CD8(+) T cells adopt a functionally attenuated state but still confer a certain degree of pathogen control. Chen et al. (2019), Hudson et al. (2019), and Zander et al. (2019) assign the lasting maintenance of this restrained pathogen control to an equilibrium of effector-like, transitory, terminal, and memory-like exhausted T cells.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Article Oncology

Metabolic and epigenetic orchestration of (CAR) T cell fate and function

Behnia Akbari, Zahra Hosseini, Pardis Shahabinejad, Saba Ghassemi, Hamid Reza Mirzaei, Roddy S. O'Connor

Summary: This article focuses on the functional impairments of CAR T cells in tumor microenvironments, where tumor cell metabolism and nutrient competition affect the differentiation and function of CAR T cells' progeny. Metabolic intermediates shape the immune response by influencing epigenetic programs.

CANCER LETTERS (2022)

添加到收藏夹

Article Cell Biology

CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Xingzhe Ma, Liuling Xiao, Lintao Liu, Lingqun Ye, Pan Su, Enguang Bi, Qiang Wang, Maojie Yang, Jianfei Qian, Qing Yi

Summary: Understanding the mechanisms of how T cells become dysfunctional in a tumor microenvironment is crucial for cancer immunotherapy. This study found that CD36 expression in tumor-infiltrating CD8(+) T cells, induced by TME cholesterol, is associated with tumor progression and poor survival, and that genetic ablation of Cd36 in these T cells leads to enhanced tumor eradication. Targeting CD36 or inhibiting ferroptosis could restore T cell function and enhance antitumor efficacy, especially in combination with anti-PD-1 antibodies.

CELL METABOLISM (2021)

添加到收藏夹

Editorial Material Immunology

The folate way to T cell fate

Paola de Candia, Giuseppe Matarese

Summary: This study reveals the role of folate-dependent one carbon metabolism enzyme MTHFD2 in CD4(+) T cell polarization and suggests its involvement in suppressing pro-inflammatory T cells while promoting regulatory T cells.

IMMUNITY (2022)

添加到收藏夹

Article Immunology

CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4+ T cells

Yuwei Hao, Bahar Miraghazadeh, Rochna Chand, Ainsley R. Davies, Chelisa Cardinez, Kristy Kwong, Morgan B. Downes, Rebecca A. Sweet, Pablo F. Canete, Lloyd J. D'Orsogna, David A. Fulcher, Sharon Choo, Desmond Yip, Geoffrey Peters, Sonia Yip, Matthew J. Witney, Maxim Nekrasov, Zhi-Ping Feng, David C. Tscharke, Carola G. Vinuesa, Matthew C. Cook

Summary: Chronic antigenic stimulation in primary antibody deficiency (PAD) patients provides insights into T-cell differentiation and how environmental exposures modify clinical phenotypes caused by single-gene defects. CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation. CD57(+) CD4(+) T cells are increased in PAD patients and significantly increased with CTLA4 haploinsufficiency or blockade, exhibiting a cytotoxic transcriptome similar to CD8(+) effector cells, killing B cells, and inhibiting B-cell responses. CTLA4 restrains the formation of cytotoxic CD4(+) T cells.

CELLULAR & MOLECULAR IMMUNOLOGY (2023)

添加到收藏夹

Article Multidisciplinary Sciences

MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection

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)

添加到收藏夹

Article Oncology

Nicotinamide Inhibits T Cell Exhaustion and Increases Differentiation of CD8 Effector T Cells

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.

CANCERS (2022)

添加到收藏夹

Article Immunology

Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development

Stefanie Scherer, Susanne G. Oberle, Kristiyan Kanev, Ann-Katrin Gerullis, Ming Wu, Gustavo P. de Almeida, Daniel J. Puleston, Francesc Baixauli, Lilian Aly, Alessandro Greco, Tamar Nizharadze, Nils B. Becker, Madlaina V. Hoesslin, Lara V. Donhauser, Jacqueline Berner, Talyn Chu, Hayley A. McNamara, Zeynep Esencan, Patrick Roelli, Christine Wurmser, Ingo Kleiter, Maria J. G. T. Vehreschild, Christoph A. Mayer, Percy Knolle, Martin Klingenspor, Valeria Fumagalli, Matteo Iannacone, Martin Prlic, Thomas Korn, Erika L. Pearce, Thomas Hoefer, Anna M. Schulz, Dietmar Zehn

Summary: The study shows that dihydroorotate dehydrogenase in the de novo pyrimidine synthesis pathway functions as a cell fate checkpoint that allows for targeted reduction of effector T cells without affecting memory T cells. Blocking pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase is effective in treating autoimmunity and preventing expansion of rapidly dividing cell populations. Early effector T cells are more susceptible to pyrimidine starvation due to their higher proliferative rate and lower pyrimidine synthesis capacity compared to memory T cell precursors. This cell fate checkpoint can potentially lead to new methods for manipulating effector T cell responses.

NATURE IMMUNOLOGY (2023)

添加到收藏夹

Article Chemistry, Multidisciplinary

Neuroendocrine Regulation of Stress-Induced T Cell Dysfunction during Lung Cancer Immunosurveillance via the Kisspeptin/GPR54 Signaling Pathway

Su Zhang, Fangfei Yu, Anran Che, Binghe Tan, Chenshen Huang, Yuxue Chen, Xiaohong Liu, Qi Huang, Wenying Zhang, Chengbin Ma, Min Qian, Mingyao Liu, Juliang Qin, Bing Du

Summary: Emerging evidence suggests that physiological distress is closely correlated with cancer incidence and mortality. This study demonstrates that acute restraint increases the levels of kisspeptin and the expression of its receptor, Gpr54, in the hypothalamus and T cells within the spleen and tumor microenvironment. The administration of kisspeptin-10 impairs T cell function, while knockout of Gpr54 inhibits lung tumor progression. These findings indicate that kisspeptin/GPR54 signaling plays a nonredundant role in stress-induced tumor immune evasion.

ADVANCED SCIENCE (2022)

添加到收藏夹

Editorial Material Cell Biology

B cell targeting in CAR T cell therapy: Side effect or driver of CAR T cell function?

Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan

Summary: CAR T cell therapies targeting CD19 and CD22 have shown success in treating B cell cancers, but not in non-B cell cancers. The interaction between CAR T cells and normal B cells may play a crucial role in determining clinical CAR T cell responses.

SCIENCE TRANSLATIONAL MEDICINE (2022)

添加到收藏夹

Review Immunology

T cell fate decisions during memory cell generation with aging

Ines Sturmlechner, Abhinav Jain, Yunmei Mu, Cornelia M. Weyand, Jorg J. Goronzy

Summary: The defense against infectious diseases relies on the generation and maintenance of protective T cell memory. However, T cell differentiation in older adults tends to generate effector cells at the expense of memory and Tfh cells. This leads to poor vaccine responses, increased inflammatory state, and shorter life spans.

SEMINARS IN IMMUNOLOGY (2023)

添加到收藏夹

Review Immunology

The Role of Metabolic Dysfunction in T-Cell Exhaustion During Chronic Viral Infection

Kehong Zheng, Xiaojun Zheng, Wei Yang

Summary: T-cell exhaustion, caused by metabolic dysfunction, impairs the ability of T cells to eliminate pathogens during chronic viral infections.

FRONTIERS IN IMMUNOLOGY (2022)

添加到收藏夹

Article Immunology

Mitochondrial-Linked De Novo Pyrimidine Biosynthesis Dictates Human T-Cell Proliferation but Not Expression of Effector Molecules

Marlies J. W. Peeters, Pia Aehnlich, Adriano Pizzella, Kasper Molgaard, Tina Seremet, Ozcan Met, Lene Juel Rasmussen, Per Thor Straten, Claus Desler

Summary: This study demonstrates the independent and important cytostatic regulation of activated T cells by DHODH and mitochondrial-linked pyrimidine synthesis. Inhibition of DHODH leads to impaired proliferation of activated T cells, which can be fully rescued by uridine supplementation.

FRONTIERS IN IMMUNOLOGY (2021)

添加到收藏夹

Review Medicine, General & Internal

CD8+ T Cell Responses during HCV Infection and HCC

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)

添加到收藏夹

Article Oncology

The dysfunctional immune response in renal cell carcinoma correlates with changes in the metabolic landscape of ccRCC during disease progression

Nicola E. Annels, M. Denyer, D. Nicol, S. Hazell, A. Silvanto, M. Crockett, M. Hussain, Carla Moller-Levet, Hardev Pandha

Summary: The study found that T-cell function in patients with renal cell carcinoma is impaired, leading to a loss of control over tumor growth. These exhausted T-cells displayed a phenotype of metabolic insufficiency and showed different characteristics at different disease stages. The down-regulation of the PPARGC1A gene may be a key factor in the progression of RCC disease, potentially affecting the effectiveness of immunotherapy and patient outcomes.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2023)

添加到收藏夹

Article Cell Biology

Loss of PBAF promotes expansion and effector differentiation of CD8+T cells during chronic viral infection and cancer

Arjun Kharel, Jian Shen, Ryan Brown, Yao Chen, Christine Nguyen, Donia Alson, Theresa Bluemn, Jie Fan, Kexin Gai, Bin Zhang, Matthew Kudek, Nan Zhu, Weiguo Cui

Summary: During chronic viral infection and cancer, a subset of progenitor CD8+ T cells continuously gives rise to terminally exhausted cells and cytotoxic effector cells. The chromatin remodeling complex PBAF plays a role in maintaining chromatin accessibility of multiple genetic pathways and transcriptional programs to restrain proliferation and promote T cell exhaustion. Perturbation of PBAF complex constrained exhaustion and promoted expansion of tumor-specific CD8+ T cells, resulting in antitumor immunity and implicating PBAF as a potential target for cancer immunotherapy.

CELL REPORTS (2023)

添加到收藏夹

Article Cell Biology

A Single-Cell Perspective on Memory T-Cell Differentiation

Lorenz Kretschmer, Dirk H. Busch, Veit R. Buchholz

Summary: This study focuses on the memory differentiation of CD4 and CD8 T-cell populations, and how regulatory principles identified on a population level translate to immune responses originating from single antigen-specific T cells. It explores the fate decisions of single T cells modulated by TCR affinity and coregulation of T-cell differentiation and proliferation, with findings indicating a key event of early segregation into distinct T central memory precursors.

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2021)

添加到收藏夹

Article Immunology

Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection

Sophie Flommersfeld, Jan P. Bottcher, Jonatan Ersching, Michael Flossdorf, Philippa Meiser, Ludwig O. Pachmayr, Justin Leube, Inge Hensel, Sebastian Jarosch, Qin Zhang, M. Zeeshan Chaudhry, Immanuel Andrae, Matthias Schiemann, Dirk H. Busch, Luka Cicin-Sain, Joseph C. Sun, Georg Gasteiger, Gabriel D. Victora, Thomas Hoefer, Veit R. Buchholz, Simon Grassmann

Summary: Upon viral infection, NK cells with specific receptors undergo an adaptive-like response, with two distinct NK cell lineages identified to contribute to this response. ILC1-like NK cells exhibit strong cytokine production, ability to recognize and kill infected cells, and bridge innate and adaptive viral recognition, showing features of both cNK cells and ILC1s.

IMMUNITY (2021)

添加到收藏夹

Editorial Material Immunology

T cell memories of past divisions

Lorenz Kretschmer, Veit R. Buchholz

Summary: A genetic recorder of T cell replicative history identifies that a subset of CD8(+) central memory T cells show fewer accumulated divisions, indicating stem-cell-like quiescence and superior recall capacity.

NATURE IMMUNOLOGY (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Heritable changes in division speed accompany the diversification of single T cell fate

Marten Plambeck, Atefeh Kazeroonian, Dirk Loeffler, Lorenz Kretschmer, Ciro Salinno, Timm Schroeder, Dirk H. Busch, Michael Flossdorf, Veit R. Buchholz

Summary: This study utilized continuous live-cell imaging to track the division speed and genealogical connections of a single naive CD8(+) T cell and its descendants. The results showed that T cell clonal expansion consists of a short burst phase with homogeneous fast division speed, followed by diversification of division speed and differentiation into memory and effector cells.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

添加到收藏夹

Article Multidisciplinary Sciences

MYB orchestrates T cell exhaustion and response to checkpoint inhibition

Carlson Tsui, Lorenz Kretschmer, Svenja Rapelius, Sarah S. Gabriel, David Chisanga, Konrad Knoepper, Daniel T. Utzschneider, Simone Nuessing, Yang Liao, Teisha Mason, Santiago Valle Torres, Stephen A. Wilcox, Krystian Kanev, Sebastian Jarosch, Justin Leube, Stephen L. Nutt, Dietmar Zehn, Ian A. Parish, Wolfgang Kastenmueller, Wei Shi, Veit R. Buchholz, Axel Kallies

Summary: This study reveals that CD62L(+) T-PEX cells, maintained by the transcription factor MYB, play a crucial role in maintaining the proliferative potential, multipotency, and repopulation capacity of exhausted T cells during chronic infection, thus contributing to long-term antiviral immunity and responsiveness to immunotherapy.

NATURE (2022)

添加到收藏夹

Article Immunology

Signatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high avidity

Anna Purcarea, Sebastian Jarosch, Jack Barton, Simon Grassmann, Ludwig Pachmayr, Elvira D'Ippolito, Monika Hammel, Anna Hochholzer, Karolin Wagner, Joost H. van den Berg, Veit R. Buchholz, John B. A. G. Haanen, Dirk H. Busch, Kilian Schober

Summary: This study investigated the fate and functionality of tumor neoantigen-specific T cells with TCRs of distinct avidities in both mice and human patients with melanoma. The findings revealed that high-avidity TCRs had the best tumor protection, but both high- and low-avidity T cells exhibited similar abundance and exhaustion within the tumor. Surprisingly, high-avidity TCR T cells were selectively enriched in T cell populations with intermediate PD-1 protein expression outside the tumor.

SCIENCE IMMUNOLOGY (2022)

添加到收藏夹

Article Immunology

Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection

Justin Leube, Anton Muehlbauer, Immanuel Andrae, Madleen Biggel, Dirk H. Busch, Lorenz Kretschmer, Veit R. Buchholz

Summary: T cell ignorance refers to the maintenance of naivety in antigen-specific T cells despite the presence of their target antigen. It is mainly observed during steady state conditions and may play a role in shaping the CD8(+) T cell responses to systemic infection by influencing the recruitment and persistence of low-affinity antigen-specific T cells. High-affinity antigen-specific CD8(+) T cells are efficiently recruited during systemic infection, while low-affinity T cells remain clonally ignorant but responsive to subsequent immunization.

EUROPEAN JOURNAL OF IMMUNOLOGY (2023)

添加到收藏夹

Article Gastroenterology & Hepatology

CagA-specific Gastric CD8D Tissue-Resident T Cells Control Helicobacter pylori During the Early Infection Phase

Maximilian R. A. Koch, Ruolan Gong, Verena Friedrich, Veronika Engelsberger, Lorenz Kretschmer, Andreas Wanisch, Sebastian Jarosch, Anna Ralser, Bob Lugen, Michael Quante, Michael Vieth, Riccardo Vasapolli, Christian Schulz, Veit R. Buchholz, Dirk H. Busch, Raquel Mejias-Luque, Markus Gerhard

Summary: This study comprehensively characterizes the CD8+ T-cell responses to Helicobacter pylori infection in mice and humans, and identifies a population of CD8+ tissue-resident memory T cells that play a crucial role in pathogen control. As the infection progresses, there is a shift in the immune response from CD8+ to CD4+ T cells.

GASTROENTEROLOGY (2023)

添加到收藏夹

Article Oncology

In vivo dynamics and anti-tumor effects of EpCAM-directed CAR T-cells against brain metastases from lung cancer

Tao Xu, Philipp Karschnia, Bruno Loureiro Cadilha, Sertac Dede, Michael Lorenz, Niklas Seewaldt, Elene Nikolaishvili, Katharina Mueller, Jens Blobner, Nico Teske, Julika J. Herold, Kai Rejeski, Sigrid Langer, Hannah Obeck, Theo Lorenzini, Matthias Mulazzani, Wenlong Zhang, Hellen Ishikawa-Ankerhold, Veit R. Buchholz, Marion Subklewe, Niklas Thon, Andreas Straube, Joerg-Christian Tonn, Sebastian Kobold, Louisa von Baumgarten

Summary: In this study, a syngeneic orthotopic cerebral metastasis model was established in mice using a chronic cranial window and repetitive intracerebral two-photon laser scanning-microscopy. The results showed that locally injected CAR T-cells could accumulate within the tumor, reduce tumor growth, and prolong survival. However, the number of CAR T-cells within the tumor decreased over time, indicating the need for strategies to improve CAR T-cell persistence.

ONCOIMMUNOLOGY (2023)

添加到收藏夹

Meeting Abstract Immunology

Single-cell fate mapping reveals widespread clonal ignorance of low affinity T cells exposed to systemic infection

J. Leube, A. Muehlbauer, I. Andrae, M. Biggel, D. Busch, L. Kretschmer, V. Buchholz

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

Meeting Abstract Immunology

Signatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high avidity

A. Purcarea, S. Jarosch, J. Barton, S. Grassmann, L. Pachmayr, E. d'Ippolito, M. Hammel, A. Hochholzer, K. I. Wagner, J. H. van den Berg, V. R. Buchholz, J. B. A. G. Haanen, D. H. Busch, K. Schober

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

Meeting Abstract Immunology

c-Myb instructs both stemness and functional exhaustion of CD8+ T cells during chronic infection

C. Tsui, L. Kretschmer, S. Rapelius, S. S. Gabriel, D. Chisanga, K. Knoepper, D. T. Utzschneider, S. Nussing, Y. Liao, T. Mason, S. V. Torres, S. A. Wilcox, K. Kanev, S. Jarosch, J. Leube, S. L. Nutt, D. Zehn, I. Parish, W. Kastenmueller, W. Shi, V. R. Buchholz, A. Kallies

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

Meeting Abstract Immunology

Transcriptional programming of cDC1 dysfunctionality by PGE2-signaling in tumor tissue disables the orchestration of protective anticancer immunity

F. Bayerl, S. Donakonda, P. Meiser, A. Hirschberger, S. Lacher, A. -M. Pedde, C. Hermann, R. Oellinger, N. Kirchhammer, M. Trefny, T. Rudolph, A. Elewaut, M. Anton, D. Wohlleber, S. Grassmann, B. Hoechst, A. Zaremba, A. Krueger, R. Rad, A. C. Obenauf, V. R. Buchholz, D. Schadendorf, A. Zippelius, C. Reis e Sousa, B. Schraml, J. P. Boettcher

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

Meeting Abstract Immunology

CD8+ T cells in H. pylori infection - phenotype, function and specificity

M. R. Koch, A. Wanisch, V. Friedrich, A. Ralser, S. Jarosch, B. Lugen, V. R. Buchholz, D. H. Busch, R. Mejias-Luque, M. Gerhard

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

Meeting Abstract Immunology

A dysfunctional program imprinted by prostaglandin E2signaling shuts off natural killer cell communication pathways and disables immunosurveillance of metastasis

A. -M. Pedde, H. Kim, S. Donakonda, F. Bayerl, P. Meiser, A. Hirschberger, C. Klement, S. Grassmann, S. Flommersfeld, G. Wiedemann, J. Trapani, M. J. Smyth, V. R. Buchholz, R. Rad, J. C. Sun, J. P. Boettcher

EUROPEAN JOURNAL OF IMMUNOLOGY (2022)

添加到收藏夹

暂无数据

© Peeref 2019-2024. All rights reserved.