We herein have provided compelling evidence that long-term ↑[H+]-conditioned CD8+ T cells showed enhanced persistence and superior anti-tumor ability in vivo, with a reduced terminally-exhausted T cell population (TCF1−TIM-3+) and increased stem-like progenitor subset (TCF1+TIM-3–) within tumors. The gene discussed is CD8A; the disease is neoplasm.