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LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells
Ist Teil von
Biochemical and biophysical research communications, 2020-07, Vol.528 (2), p.330-335
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2020
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Radiotherapy (RT) is an important radical treatment for locally advanced non-small cell lung cancer (NSCLC). However, radioresistance greatly impairs the efficacy of this therapy in the clinic. Radioresistance can be caused by radiation-induced myeloid-derived suppressor cell (MDSC) infiltration. Liver-X nuclear receptor (LXR) agonists have demonstrated potent antitumor activity in preclinic animal models. Here, we report for the first time that LXR agonists, GW3965 and RGX-104, radiosensitized NSCLC in a subcutaneous homograft murine model. LXR activation significantly reduced MDSC abundance in the tumor microenvironment (TME). Treatment with RGX-104 greatly promoted MDSC apoptosis in vitro. Depleting MDSC activated cytotoxic T lymphocyte (CTL) and T-helper 1 (Th1) responses in the TME. In conclusion, the immunosuppressive effects of radiotherapy can be abrogated partly with an LXR agonist by depleting MDSC, which sensitizes NSCLC to RT.
•Radiotherapy increases the infiltration of MDSCs in tumors.•LXR agonists reduce MDSC in tumor microenvironment by killing MDSC directly.•LXR agonists augmente anti-tumor immune response and radiosensitize NSCLC.•Combination of LXR agonists and radiotherapy can significantly prolong the survival time of tumor-bearing mice.