RT Journal Article SR Electronic T1 Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids JF Cancer Discovery JO Cancer Discov FD American Association for Cancer Research SP 196 OP 215 DO 10.1158/2159-8290.CD-17-0833 VO 8 IS 2 A1 Jenkins, Russell W. A1 Aref, Amir R. A1 Lizotte, Patrick H. A1 Ivanova, Elena A1 Stinson, Susanna A1 Zhou, Chensheng W. A1 Bowden, Michaela A1 Deng, Jiehui A1 Liu, Hongye A1 Miao, Diana A1 He, Meng Xiao A1 Walker, William A1 Zhang, Gao A1 Tian, Tian A1 Cheng, Chaoran A1 Wei, Zhi A1 Palakurthi, Sangeetha A1 Bittinger, Mark A1 Vitzthum, Hans A1 Kim, Jong Wook A1 Merlino, Ashley A1 Quinn, Max A1 Venkataramani, Chandrasekar A1 Kaplan, Joshua A. A1 Portell, Andrew A1 Gokhale, Prafulla C. A1 Phillips, Bart A1 Smart, Alicia A1 Rotem, Asaf A1 Jones, Robert E. A1 Keogh, Lauren A1 Anguiano, Maria A1 Stapleton, Lance A1 Jia, Zhiheng A1 Barzily-Rokni, Michal A1 Cañadas, Israel A1 Thai, Tran C. A1 Hammond, Marc R. A1 Vlahos, Raven A1 Wang, Eric S. A1 Zhang, Hua A1 Li, Shuai A1 Hanna, Glenn J. A1 Huang, Wei A1 Hoang, Mai P. A1 Piris, Adriano A1 Eliane, Jean-Pierre A1 Stemmer-Rachamimov, Anat O. A1 Cameron, Lisa A1 Su, Mei-Ju A1 Shah, Parin A1 Izar, Benjamin A1 Thakuria, Manisha A1 LeBoeuf, Nicole R. A1 Rabinowits, Guilherme A1 Gunda, Viswanath A1 Parangi, Sareh A1 Cleary, James M. A1 Miller, Brian C. A1 Kitajima, Shunsuke A1 Thummalapalli, Rohit A1 Miao, Benchun A1 Barbie, Thanh U. A1 Sivathanu, Vivek A1 Wong, Joshua A1 Richards, William G. A1 Bueno, Raphael A1 Yoon, Charles H. A1 Miret, Juan A1 Herlyn, Meenhard A1 Garraway, Levi A. A1 Van Allen, Eliezer M. A1 Freeman, Gordon J. A1 Kirschmeier, Paul T. A1 Lorch, Jochen H. A1 Ott, Patrick A. A1 Hodi, F. Stephen A1 Flaherty, Keith T. A1 Kamm, Roger D. A1 Boland, Genevieve M. A1 Wong, Kwok-Kin A1 Dornan, David A1 Paweletz, Cloud Peter A1 Barbie, David A. YR 2018 UL http://cancerdiscovery.aacrjournals.org/content/8/2/196.abstract AB 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