Abstract 848: Galectin-1 mediates radiation-related lymphopenia in non-small cell lung cancer and attenuates tumor radiation response

Abstract

Abstract Decreased circulating lymphocytes after tumor irradiation has been linked to worse outcomes in several cancers treated with fractionated radiotherapy. The mechanism underlying radiation (RT)-induced lymphopenia is not well understood. Here, we show that lymphopenia also occurs after stereotactic ablative radiotherapy for early stage non-small cell lung cancer, and that it is associated with reduced survival. We provide evidence that RT-induced secretion of Galectin-1 (Gal-1), a b-galactoside binding protein, can potentially explain for this phenomenon. Using matched Gal-1 wild type and null mice together with Lewis lung carcinoma cells stably knocked-down of Gal-1 or scramble control, we show that irradiation of Gal-1 expressing tumor increases Gal-1 secretion in the blood and that it is linked to decreased circulating T-lymphocytes. This was ablated by either genetic down regulation of Gal-1 in the tumor or inhibition of Gal-1 activity by TDG. Moreover, Gal-1 down regulation resulted in enhanced radiation sensitivity in vitro as well as less intratumoral T cell apoptosis and angiogenesis in vivo, resulting in marked tumor growth delay and reduced spontaneous lung metastases when combined with radiotherapy. Similar results were noted when Gal-1 function was inhibited with TDG in vivo. Together, our data identify Gal-1 as an important mediator of RT-related lymphopenia and its proangiogenic and T cell proapototic effect may explain for the poorer outcome associated with RT-related lymphopenia. Gal-1 is therefore a new potential therapeutic target to combine with radiotherapy. Citation Format: Peiwen Kuo, Scott Bratman, David Shultz, Rie von Eyben, Cato Chan, Ziwei Wang, Carmen Say, Aparna Gupta, Bill W. Loo, Amato Giaccia, Albert Koong, Maximilian Diehn, Quynh-Thu Le. Galectin-1 mediates radiation-related lymphopenia in non-small cell lung cancer and attenuates tumor radiation response. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 848. doi:10.1158/1538-7445.AM2014-848