Adoptive Transfer of ILC2s into the Brain Reveals Tumor Homing in Glioblastoma: A Proof-of-Concept for Cellular Therapy

Abstract

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor immune cell infiltration. Cellular immunotherapies have transformed cancer treatment but remain largely ineffective against GBM due to the restrictive blood-brain barrier (BBB) and its profoundly immunosuppressive microenvironment. Innate lymphoid cells type 2 (ILC2s) have recently emerged as potential candidates for cellular immunotherapy because of their regenerative and immunomodulatory functions. Here, we provide the first in vivo evidence that systemically administered ILC2s can cross the BBB and home to glioblastoma. Bone marrow-derived ILC2s from C57BL/6 mice were labeled with CFSE and intravenously transferred into hosts bearing orthotopic, luciferase-expressing GL261 tumors. Fluorescence imaging and flow cytometry analyses indicated that transferred ILC2s successfully entered the brain, localized within tumor tissue, and were also detected in meninges and peripheral organs. Although no measurable reduction in tumor growth was observed, these findings support a proof-of-concept for adoptive ILC2 transfer as a feasible approach for targeting CNS tumors and exploring their immunomodulatory potential in GBM.