Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia
Qing Zhou,Meghan E. Munger,Rachelle G. Veenstra,Brenda J. Weigel,Mitsuomi Hirashima,David H. Munn,William J. Murphy,Miyuki Azuma,Ana C. Anderson,Vijay K. Kuchroo,Bruce R. Blazar +10 more
TLDR
Combined PD-1/PDL1 and Tim-3/galectin-9 blockade may be beneficial in preventing CD8(+) T-cell exhaustion in patients with hematologic malignancies such as advanced AML.About:
This article is published in Blood.The article was published on 2011-04-28 and is currently open access. It has received 544 citations till now. The article focuses on the topics: Cytotoxic T cell & CD8.read more
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Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation
TL;DR: Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co- inhibitory receptor expression on T cells dampens effector T-cell responses.
Journal ArticleDOI
4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors
Adrienne H. Long,Waleed Haso,Jack F. Shern,Kelsey Wanhainen,Meera Murgai,Maria Ingaramo,Jillian P. Smith,Alec J. Walker,M. Eric Kohler,Vikas R Venkateshwara,Rosandra N. Kaplan,George H. Patterson,Terry J. Fry,Rimas J. Orentas,Crystal L. Mackall +14 more
TL;DR: It is shown that tonic CAR CD3-ζ phosphorylation, triggered by antigen-independent clustering of CAR single-chain variable fragments, can induce early exhaustion of CAR T cells that limits antitumor efficacy, and that CD28 costimulation augments, whereas 4-1BB costimulations reduces, exhaustion induced by persistent CAR signaling.
Journal ArticleDOI
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity.
TL;DR: Encouraging early clinical results using blocking agents against components of the PD-1 pathway have validated its importance as a target for cancer immunotherapy.
Journal ArticleDOI
Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.
Shohei Koyama,Esra A. Akbay,Yvonne Y. Li,Grit S. Herter-Sprie,Kevin A. Buczkowski,William G. Richards,Leena Gandhi,Amanda J. Redig,Scott J. Rodig,Hajime Asahina,Robert E. Jones,Meghana M. Kulkarni,Mari Kuraguchi,Sangeetha Palakurthi,Peter E. Fecci,Bruce E. Johnson,Pasi A. Jänne,Jeffrey A. Engelman,Sidharta P. Gangadharan,Daniel B. Costa,Gordon J. Freeman,Raphael Bueno,F. Stephen Hodi,Glenn Dranoff,Kwok-Kin Wong,Peter S. Hammerman,Peter S. Hammerman +26 more
TL;DR: Analysis of the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma suggests that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.
Journal ArticleDOI
CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review.
TL;DR: CD8 + T cell priming is directed essentially as a corroboration work between cells of innate immunity including dendritic cells (DCs) and natural killer (NK) cells with CD4 + T cells in adoptive immunity for making durable and efficient antitumor immune responses.
References
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Journal ArticleDOI
Restoring function in exhausted CD8 T cells during chronic viral infection.
Daniel L. Barber,E. John Wherry,David Masopust,Baogong Zhu,James P. Allison,Arlene H. Sharpe,Gordon J. Freeman,Rafi Ahmed +7 more
TL;DR: In this article, the authors analyzed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus (LCMV), and compared these with the gene profile of functional memory CD8T cells.
Journal Article
Restoring function in exhausted CD8 T cells during chronic viral infection
TL;DR: It is found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the ‘helpless’ CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load.
Journal ArticleDOI
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Cheryl L. Day,Daniel Kaufmann,Photini Kiepiela,Julia A. Brown,Eshia Moodley,Sharon Reddy,Elizabeth W Mackey,Joseph D. Miller,Alasdair Leslie,Chantal DePierres,Zenele Mncube,Jaikumar Duraiswamy,Baogong Zhu,Quentin Eichbaum,Marcus Altfeld,E. John Wherry,Hoosen M. Coovadia,Philip J. R. Goulder,Philip J. R. Goulder,Philip J. R. Goulder,Paul Klenerman,Rafi Ahmed,Gordon J. Freeman,Bruce D. Walker,Bruce D. Walker,Bruce D. Walker +25 more
TL;DR: The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.
Journal ArticleDOI
Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Allan J. Zajac,Joseph N. Blattman,Kaja Murali-Krishna,David J. D. Sourdive,M. Suresh,John D. Altman,Rafi Ahmed +6 more
TL;DR: The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancingCD8 T cell immunity in chronically infected hosts.
Journal ArticleDOI
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
E. John Wherry,Sang Jun Ha,Susan M. Kaech,W. Nicholas Haining,Surojit Sarkar,Vandana Kalia,Shruti Subramaniam,Joseph N. Blattman,Daniel L. Barber,Rafi Ahmed +9 more
TL;DR: T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes, which provides a framework for designing rational immunotherapies during chronic infections.
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