M2 type tumor-associated macrophage-derived CCL-18 promotes glioma cell proliferation but does not mediates glioma recurrence after radiotherapy.

Most of glioma patients still experience relapse after radiotherapy owing to the formation of tumor immunosuppressive microenvironment. However, the comprehensive landscape of immune cell infiltration and the molecular mechanisms mediating glioma recurrence remains unclear. Bulk RNA sequencing (RNA-seq) analysis revealed the significant changes in the immune system including increased total tumor-associated macrophages (TAMs) and elevated M2-TAMs in recurrent glioma accepting radiotherapy. Meanwhile, C-C motif chemokine 18 (CCL-18) was the highest elevated molecule after radiotherapy. Consistently, the aforementioned results were confirmed in tissue microarray containing 23 paired gliomas. In vitro, radiation promoted TAM polarization into M2-TAMs, accompanying CCL-18 secretion. However, CCL-18 promoted non-irradiated glioma proliferation but did not mediate glioma recurrence after radiotherapy. Mechanistically, the pro-tumor effect of CCL-18 was weakened by the down-regulation of CCL-18 receptors on glioma accepting radiotherapy. Our study indicates CCL-18 does not mediate glioma recurrence but has the potential to serve as a biomarker for recurrent gliomas.