title: Compartment-Specific Bioluminescence Imaging platform for the high-throughput evaluation of antitumor immune function.
abstract: Conventional assays evaluating antitumor activity of immune effector cells have limitations that preclude their high-throughput application. We adapted the recently developed Compartment-Specific Bioluminescence Imaging (CS-BLI) technique to perform high-throughput quantification of innate antitumor activity and to show how pharmacologic agents (eg, lenalidomide, pomalidomide, bortezomib, and dexamethasone) and autologous BM stromal cells modulate that activity. CS-BLI-based screening allowed us to identify agents that enhance or inhibit innate antitumor cytotoxicity. Specifically, we identified compounds that stimulate immune effector cells against some tumor targets but suppressed their activity against other tumor cells. CS-BLI offers rapid, simplified, and specific evaluation of multiple conditions, including drug treatments and/or cocultures with stromal cells and highlights that immunomodulatory pharmacologic responses can be heterogeneous across different types of tumor cells. This study provides a framework to identify novel immunomodulatory agents and to prioritize compounds for clinical development on the basis of their effect on antitumor immunity.
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: McMillin
authors.forename: Jake
authors.initials: J
authors.lastname: Delmore
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Negri
authors.forename: Matthew
authors.initials: M
authors.lastname: Vanneman
authors.forename: Shohei
authors.initials: S
authors.lastname: Koyama
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schlossman
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002470:Cell Survival; D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007167:Immunotherapy / Q000379:methods; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008163:Luminescent Measurements / Q000295:instrumentation / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013379:Substrate Specificity / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D019002:CD56 Antigen