T-Cell Dysfunction in Glioblastoma: Applying a New Framework

A functional, replete T cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive anti-tumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging anti-tumor immunity, eliciting severe T cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anti-cancer immune-based therapies. While T cell dysfunction in GBM is long described, newer immunologic frameworks now exist for re-classifying T cell deficits in a manner that better permits their study and reversal. Herein, we divide and discuss the various T cell deficits elicited by GBM within the context of the five relevant categories - Senescence, Tolerance, Anergy, Exhaustion, and Ignorance. Categorization is appropriately made according to the molecular bases of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode of T cell dysfunction and discuss the emerging immunotherapeutic strategies designed to overcome them.

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