American Association for Cancer Research
10780432ccr141138-sup-131141_1_supp_2571078_n90vxm.png (125.44 kB)

Supplementary Figure 1 from Galectin-1 Mediates Radiation-Related Lymphopenia and Attenuates NSCLC Radiation Response

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posted on 2023-03-31, 19:00 authored by Peiwen Kuo, Scott V. Bratman, David B. Shultz, Rie von Eyben, Cato Chan, Ziwei Wang, Carmen Say, Aparna Gupta, Bill W. Loo, Amato J. Giaccia, Albert C. Koong, Maximilian Diehn, Quynh-Thu Le

A schematic of tumor/host combinations showing Gal-1 WT and null C57Bl6/mice subcutaneous injection with Wt and shGal-1 LLC1 cells, time line of cell injection, tumor irradiation and blood collection time points. The relative plasma Gal-1 levels for each treatment group is also shown.



Purpose: Radiotherapy can result in lymphopenia, which has been linked to poorer survival. Here, we test the hypothesis that radiotherapy-induced lymphopenia is mediated by a tumor-secreted factor, Galectin-1 (Gal-1), which possesses T-cell proapoptotic activities.Experimental Design: Matched Gal-1 wild-type (WT) or null mice were implanted with Lewis lung carcinoma (LLC-1) that either expressed Gal-1 or had Gal-1 stably downregulated. Tumors were irradiated locally and circulating Gal-1 and T cells were measured. Tumor growth, lung metastasis, intratumoral T-cell apoptosis, and microvessel density count were quantified. Thiodigalactoside (TDG), a Gal-1 inhibitor, was used to inhibit Gal-1 function in another group of mice to validate the observations noted with Gal-1 downregulation. Lymphocyte counts, survival, and plasma Gal-1 were analyzed in cohorts of radiotherapy-treated lung [non–small cell lung cancer (NSCLC)] and head and neck cancer patients.Results: LLC irradiation increased Gal-1 secretion and decreased circulating T cells in mice, regardless of host Gal-1 expression. Inhibition of tumor Gal-1 with either shRNA or thiodigalactoside ablated radiotherapy-induced lymphopenia. Irradiated shGal-1 tumors showed significantly less intratumoral CD8+ T-cell apoptosis and microvessel density, which led to marked tumor growth delay and reduced lung metastasis compared with controls. Similar observations were made after thiodigalactoside treatment. Radiotherapy-induced lymphopenia was associated with poorer overall survival in patients with NSCLC treated with hypofractionated radiotherapy. Plasma Gal-1 increased whereas T-cell decreased after radiation in another group of patients.Conclusions: Radiotherapy-related systemic lymphopenia appeared to be mediated by radiotherapy-induced tumor Gal-1 secretion that could lead to tumor progression through intratumoral immune suppression and enhanced angiogenesis. Clin Cancer Res; 20(21); 5558–69. ©2014 AACR.