Decoding the spatiotemporal dynamics of T cell immune landscapes in glioblastoma: remodeling precision combination therapies.

The profound intratumoral heterogeneity and the highly dynamic spatiotemporal evolution of its immunosuppressive microenvironment in glioblastoma (GBM) are major factors underlying the limited efficacy of the standard-of-care treatment (SOC). Although immunotherapy has revolutionized the treatment of many solid tumors, it has produced limited clinical benefit in patients with GBM. This limited efficacy is closely associated with the abundance, distribution, and functional state of T cells, which constitute the core effector population mediating antitumor immune responses. However, previous studies have largely focused on the static characteristics of T cells in GBM, whereas the mechanisms governing their spatiotemporal dynamics remain poorly defined, thereby impeding clinical translation. In this review, we delineate the spatiotemporal dynamics of T cells in GBM and re-evaluate the mechanisms underlying immunotherapy failure, thereby identifying potential therapeutic opportunities. Furthermore, we aim to provide new insights into patient stratification, the development of precise targets that modulate T-cell spatiotemporal dynamics, and personalized combination strategies for patients with GBM.