Several groups used this technology and have revealed that skewed T-cell clonotypes have a high expression of well-known exhaustion signature molecules such as PD-1, LAG-3, TIM-3, 4–1BB, CD39, and CD103, and such exhausted T-cell clonotypes are speculated to attack tumor cells directly (tumor-specific T cells; refs. 26, 27). This evidence concerns the gene PDCD1 and neoplasm.