Adoptive Cell Therapies for Glioblastoma: A Quest for Cures from Within

Glioblastomas (GBMs) are the most aggressive form of brain cancer recalcitrant to both current standard-of-care and immune checkpoint therapies that benefit other cancer patients. Adoptive cell therapies (ACT) using patients’ own immune cells have long been explored as a treatment strategy, including the historically studied lymphokine-activated killer (LAK) cells, the evolving chimeric antigen receptor (CAR) directed immune cells, the newly emerging tumor-infiltrating T lymphocyte (TIL) therapies, and others. Preclinical and clinical studies have shown promise but also highlighted significant challenges. In this review, we summarize these findings, highlight recent developments, discuss current limitations, and emphasize how ACT may benefit from contemporary and future insights into the co-evolution of TILs with other cells within the GBM tumor microenvironment (TME).