Immune-Related Gene Expression Profiling After PD-1 Blockade in Non–Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma
Aleix Prat,Alejandro Navarro,Laia Paré,Noemi Reguart,Patricia Galván,Tomás Pascual,A. Martinez,Paolo Nuciforo,Laura Comerma,Llucia Alos,N. Pardo,Susana Cedres,Cheng Fan,Joel S. Parker,Lydia Gaba,Iván Victoria,Nuria Viñolas,Ana Vivancos,Ana Arance,Enriqueta Felip +19 more
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TLDR
The hypothesis that identification of a preexisting and stable adaptive immune response as defined by mRNA expression pattern is reproducible and sufficient to predict clinical outcome is supported, regardless of the type of cancer or the PD1 therapeutic antibody administered to patients.Citations
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Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response
Peng Jiang,Shengqing Gu,Deng Pan,Jingxin Fu,Avinash Das Sahu,Xihao Hu,Ziyi Li,Nicole Traugh,Xia Bu,Bo Li,Bo Li,Jun Liu,Gordon J. Freeman,Myles Brown,Kai W. Wucherpfennig,X. Shirley Liu +15 more
TL;DR: An algorithm-selected gene signature focused on tumor immune evasion and suppression predicts response to immune checkpoint blockade in melanoma, exceeding the accuracy of current clinical biomarkers.
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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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Cancer immunoediting and resistance to T cell-based immunotherapy
Jake S. O’Donnell,Jake S. O’Donnell,Michele W.L. Teng,Michele W.L. Teng,Mark J. Smyth,Mark J. Smyth +5 more
TL;DR: How a deeper understanding of the mechanisms underlying the cancer immunoediting process can provide insight into the development of resistance to immunotherapies and the strategies that can be used to overcome such resistance is discussed.
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Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma.
Andrew L. Ji,Adam J. Rubin,Kim Thrane,Sizun Jiang,David Reynolds,Robin M. Meyers,Margaret Guo,Benson M. George,Annelie Mollbrink,Joseph Bergenstråhle,Ludvig Larsson,Yunhao Bai,Bokai Zhu,Aparna Bhaduri,Jordan M. Meyers,Xavier Rovira-Clavé,S. Tyler Hollmig,Sumaira Z. Aasi,Garry P. Nolan,Joakim Lundeberg,Paul A. Khavari,Paul A. Khavari +21 more
TL;DR: To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin were combined.
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Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
Noam Auslander,Gao Zhang,Joo Sang Lee,Joo Sang Lee,Dennie T. Frederick,Benchun Miao,Tabea Moll,Tian Tian,Zhi Wei,Sanna Madan,Sanna Madan,Ryan J. Sullivan,Genevieve M. Boland,Keith T. Flaherty,Meenhard Herlyn,Eytan Ruppin,Eytan Ruppin +16 more
TL;DR: IMPRES is a predictor of ICB response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes and achieves an overall accuracy of AUC = 0.83, outperforming existing predictors and capturing almost all true responders while misclassifying less than half of the nonresponders.
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TL;DR: Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1, ≥5%, and ≥10%) of the PD-1 ligand.
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