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.
journal_name
Bloodjournal_title
Bloodauthors
McMillin DW,Delmore J,Negri JM,Vanneman M,Koyama S,Schlossman RL,Munshi NC,Laubach J,Richardson PG,Dranoff G,Anderson KC,Mitsiades CSdoi
10.1182/blood-2011-04-348490subject
Has Abstractpub_date
2012-04-12 00:00:00pages
e131-8issue
15eissn
0006-4971issn
1528-0020pii
blood-2011-04-348490journal_volume
119pub_type
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