Data from <i>Ex Vivo</i> Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids
Authors: Jenkins Russell W. , Aref Amir R. , Lizotte Patrick H. , Ivanova Elena , Stinson Susanna , Zhou Chensheng W. , Bowden Michaela , Deng Jiehui , Liu Hongye , Miao Diana , He Meng Xiao , Walker William , Zhang Gao , Tian Tian , Cheng Chaoran , Wei Zhi , Palakurthi Sangeetha , Bittinger Mark , Vitzthum Hans , Kim Jong Wook , Merlino Ashley , Quinn Max , Venkataramani Chandrasekar , Kaplan Joshua A. , Portell Andrew , Gokhale Prafulla C. , Phillips Bart , Smart Alicia , Rotem Asaf , Jones Robert E. , Keogh Lauren , Anguiano Maria , Stapleton Lance , Jia Zhiheng , Barzily-Rokni Michal , Cañadas Israel , Thai Tran C. , Hammond Marc R. , Vlahos Raven , Wang Eric S. , Zhang Hua , Li Shuai , Hanna Glenn J. , Huang Wei , Hoang Mai P. , Piris Adriano , Eliane Jean-Pierre , Stemmer-Rachamimov Anat O. , Cameron Lisa , Su Mei-Ju , Shah Parin , Izar Benjamin , Thakuria Manisha , LeBoeuf Nicole R. , Rabinowits Guilherme , Gunda Viswanath , Parangi Sareh , Cleary James M. , Miller Brian C. , Kitajima Shunsuke , Thummalapalli Rohit , Miao Benchun , Barbie Thanh U. , Sivathanu Vivek , Wong Joshua , Richards William G. , Bueno Raphael , Yoon Charles H. , Miret Juan , Herlyn Meenhard , Garraway Levi A. , Van Allen Eliezer M. , Freeman Gordon J. , Kirschmeier Paul T. , Lorch Jochen H. , Ott Patrick A. , Hodi F. Stephen , Flaherty Keith T. , Kamm Roger D. , Boland Genevieve M. , Wong Kwok-Kin , Dornan David , Paweletz Cloud Peter , Barbie David A. 
Published: March 2024

<div>Abstract<p><i>Ex vivo</i> 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 <i>ex vivo</i> 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 <i>in vivo</i>. 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.</p><p><b>Significance:</b> Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of <i>ex vivo</i> profiling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts. <i>Cancer Discov; 8(2); 196–215. ©2017 AACR.</i></p><p><i>See related commentary by Balko and Sosman, p. 143</i>.</p><p><i>See related article by Deng et al., p. 216</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 127</i></p></div>