Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation
TLDR
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.About:
This article is published in Immunity.The article was published on 2016-05-17 and is currently open access. It has received 1392 citations till now. The article focuses on the topics: TIGIT & Receptor expression.read more
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Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.
TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
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Determining cell type abundance and expression from bulk tissues with digital cytometry.
Aaron M. Newman,Chloé B. Steen,Chloé B. Steen,Chih Long Liu,Andrew J. Gentles,Aadel A. Chaudhuri,Florian Scherer,Michael S. Khodadoust,Mohammad Shahrokh Esfahani,Bogdan A. Luca,David F. Steiner,Maximilian Diehn,Ash A. Alizadeh +12 more
TL;DR: The utility of CIBERSORTx is evaluated in multiple tumor types, including melanoma, where single-cell reference profiles were used to dissect bulk clinical specimens, revealing cell-type-specific phenotypic states linked to distinct driver mutations and response to immune checkpoint blockade.
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A guide to cancer immunotherapy: from T cell basic science to clinical practice.
TL;DR: This guide to cancer immunotherapy provides a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation.
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Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma.
Moshe Sade-Feldman,Moshe Sade-Feldman,Keren Yizhak,Stacey L. Bjorgaard,Stacey L. Bjorgaard,John P. Ray,Carl G. de Boer,Russell W. Jenkins,David J. Lieb,Jonathan H. Chen,Jonathan H. Chen,Dennie T. Frederick,Michal Barzily-Rokni,Samuel S. Freeman,Alexandre Reuben,Paul Hoover,Paul Hoover,Alexandra-Chloé Villani,Alexandra-Chloé Villani,Elena Ivanova,Andrew Portell,Patrick H. Lizotte,Amir Reza Aref,Jean Pierre Eliane,Marc R. Hammond,Hans Vitzthum,Shauna M. Blackmon,Bo Li,Bo Li,Vancheswaran Gopalakrishnan,Sangeetha M. Reddy,Zachary A. Cooper,Cloud P. Paweletz,David A. Barbie,Anat Stemmer-Rachamimov,Keith T. Flaherty,Jennifer A. Wargo,Genevieve M. Boland,Ryan J. Sullivan,Gad Getz,Nir Hacohen,Nir Hacohen +41 more
TL;DR: The study of immune cell transcriptomes from tumors demonstrates a strategy for identifying predictors, mechanisms, and targets for enhancing checkpoint immunotherapy by targeting novel combinations of factors in exhausted cells.
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Immunotherapy in colorectal cancer: rationale, challenges and potential.
Karuna Ganesh,Zsofia K. Stadler,Andrea Cercek,Robin B. Mendelsohn,Jinru Shia,Neil H. Segal,Luis A. Diaz +6 more
TL;DR: Clinical development of immune checkpoint inhibition in CRC leading to regulatory approvals for the treatment of dMMR–MSI-H CRC is reviewed and new advances in expanding the efficacy of immunotherapy to early-stage CRC and CRC that is mismatch-repair-proficient and has low microsatellite instability (pMMR- MSI-L) are focused on.
References
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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
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Pembrolizumab versus Ipilimumab in Advanced Melanoma
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The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
Noa Stanietsky,Hrvoje Šimić,Jurica Arapović,Amir Toporik,Ofer Levy,Amit Novik,Zurit Levine,Meirav Beiman,Liat Dassa,Hagit Achdout,Noam Stern-Ginossar,Pinhas Tsukerman,Stipan Jonjić,Ofer Mandelboim +13 more
TL;DR: It is shown that TIGIT is expressed by all human NK cells, that it binds PVR and PVRL2 but not PVRL3 and that it inhibits NK cytotoxicity directly through its ITIM, providing an “alternative self” mechanism for MHC class I inhibition.
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Molecular and cellular insights into T cell exhaustion
E. John Wherry,Makoto Kurachi +1 more
TL;DR: Recent advances that provide a clearer molecular understanding of T cell exhaustion are reviewed and reveal new therapeutic targets for persisting infections and cancer.
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