Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Blood. 2012 Apr 12;119(15):e131-8. doi: 10.1182/blood-2011-04-348490. Epub 2012 Jan 30.
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.
传统的评估免疫效应细胞抗肿瘤活性的检测方法存在局限性，不适合高通量应用。我们采用了最近开发的分区特异性生物发光成像（CS-BLI）技术，对固有抗肿瘤活性进行高通量定量，并展示了药理试剂（如来那度胺、泊马度胺、硼替佐米和地塞米松）和自体 BM 基质细胞如何调节这种活性。基于 CS-BLI 的筛选使我们能够识别增强或抑制固有抗肿瘤细胞毒性的试剂。具体来说，我们确定了刺激免疫效应细胞针对某些肿瘤靶标但抑制其对其他肿瘤细胞活性的化合物。CS-BLI 提供了快速、简化和特异性的多种条件评估，包括药物治疗和/或与基质细胞的共培养，并强调免疫调节药理反应在不同类型的肿瘤细胞之间可能存在异质性。本研究为鉴定新型免疫调节试剂以及根据其对抗肿瘤免疫的影响为临床开发确定化合物优先级提供了一个框架。
