Provided herein are compositions and methods for detecting and/or targeting dysfunctional tumor antigen-specific CD8+ T cells in the tumor microenvironment for diagnostic, therapeutic and/or research applications. In particular, dysfunctional tumor antigen-specific CD8+ T cells are detected and/or targeted via their expression of cell surface receptors described herein, such as 4-1BB, LAG-3, or additional markers that correlate with 4-1BB and LAG-3 expression, such as markers differentially expressed on the surface of the T cells.
