21598290cd170833-sup-186804_2_supp_4355523_7yg27l.xlsx (182.7 kB)

Table S2 from Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

dataset

posted on 2023-04-03, 21:21 authored by Russell W. Jenkins, Amir R. Aref, Patrick H. Lizotte, Elena Ivanova, Susanna Stinson, Chensheng W. Zhou, Michaela Bowden, Jiehui Deng, Hongye Liu, Diana Miao, Meng Xiao He, William Walker, Gao Zhang, Tian Tian, Chaoran Cheng, Zhi Wei, Sangeetha Palakurthi, Mark Bittinger, Hans Vitzthum, Jong Wook Kim, Ashley Merlino, Max Quinn, Chandrasekar Venkataramani, Joshua A. Kaplan, Andrew Portell, Prafulla C. Gokhale, Bart Phillips, Alicia Smart, Asaf Rotem, Robert E. Jones, Lauren Keogh, Maria Anguiano, Lance Stapleton, Zhiheng Jia, Michal Barzily-Rokni, Israel Cañadas, Tran C. Thai, Marc R. Hammond, Raven Vlahos, Eric S. Wang, Hua Zhang, Shuai Li, Glenn J. Hanna, Wei Huang, Mai P. Hoang, Adriano Piris, Jean-Pierre Eliane, Anat O. Stemmer-Rachamimov, Lisa Cameron, Mei-Ju Su, Parin Shah, Benjamin Izar, Manisha Thakuria, Nicole R. LeBoeuf, Guilherme Rabinowits, Viswanath Gunda, Sareh Parangi, James M. Cleary, Brian C. Miller, Shunsuke Kitajima, Rohit Thummalapalli, Benchun Miao, Thanh U. Barbie, Vivek Sivathanu, Joshua Wong, William G. Richards, Raphael Bueno, Charles H. Yoon, Juan Miret, Meenhard Herlyn, Levi A. Garraway, Eliezer M. Van Allen, Gordon J. Freeman, Paul T. Kirschmeier, Jochen H. Lorch, Patrick A. Ott, F. Stephen Hodi, Keith T. Flaherty, Roger D. Kamm, Genevieve M. Boland, Kwok-Kin Wong, David Dornan, Cloud Peter Paweletz, David A. Barbie

In vitro kinase inhibitory activity of Compound 1

Funding

Robert A. and Renée E. Belfer Foundation

NCI

John R. Svenson Fellowship

Gloria T. Maheu and Heerwagen Family Funds for Lung Cancer Research

Rising Tide Foundation

Expect Miracles Foundation

NIGMS

NSF GRFP

Caja Navarra Foundation

Excellence Doctoral Mobility Grant

Association of Friends of the University of Navarra

Doctoral Mobility Grant

NIH/NCI

Gross-Loh Family Fund for Lung Cancer Research

Susan Spooner Family Lung Cancer Research Fund

Elizabeth and Michael Ruane Fund

NIH

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

Melanoma Research Foundation

Cancer Center Support Grant (CCSG)

National Cancer Institute

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American Cancer Society Lung Cancer Dream Team Translational Research Grant

History

ARTICLE ABSTRACT

Ex vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/IKKϵ inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response in vivo. Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens.Significance: Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of ex vivo profiling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts. Cancer Discov; 8(2); 196–215. ©2017 AACR.See related commentary by Balko and Sosman, p. 143.See related article by Deng et al., p. 216.This article is highlighted in the In This Issue feature, p. 127

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Keywords

Immunology Immune responses to cancer Tumor resistance to immune response

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CC BY

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