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

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…

• NS
  National Science Foundation

  Award: NSF GRFP DGE1144152
• SU
  Stand Up To Cancer

  Award: SU2C-AACR-DT17-15
• NC
  National Cancer Institute

  Awards: 5R01CA122794-10, 5R01CA163896-04, NCI T32 CA009172-41, 5R01CA140594-07, NCI-R01 CA190394-01, 1R01CA149738-01, P01CA120964, 5R01CA166480-04
• NI
  National Institute of General Medical Sciences

  Award: NIGMS T32 GM008313