作者
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
发表日期
2018/2/1
期刊
Cancer discovery
卷号
8
期号
2
页码范围
196-215
出版商
American Association for Cancer Research
简介
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 …
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RW Jenkins, AR Aref, PH Lizotte, E Ivanova, S Stinson… - Cancer discovery, 2018