Tumor-infiltrating CD62L+PD-1-CD8 T cells retain proliferative potential via Bcl6 expression and replenish effector T cells within the tumor

Tumor antigen-primed CD8 T cells differentiate into effector T cells that kill tumor cells rapidly, whereas durable responses of CD8 T cells are required to cope with long-lasting tumor growth. However, it is not well known how persisting CD8 T cells are generated. In this study, we analyzed CD8 T cells primed by antigens in tumor-draining lymph nodes and found that CD8 T cells first differentiated into a CD62L-intermediate (CD62L(int)) stage upon antigen stimulation. These cells gave rise to tumor-infiltrating CD62L(-)CD44(high)Bcl6(-)effector T cells and CD62L(+)CD44(high)Bcl6(+)memory-like T cells. Memory-like T cells within the tumor expressed CD127, CXCR3 and had the potential to proliferate significantly when they were transferred into tumor-bearing mice. Bcl6 expression in these T cells was critical because Bcl6(-/-)CD62L(+)CD44(high)CD8T cells within the tumor were defective in expansion after secondary transfer. Taken together, our findings show that CD62L(+)CD44(high)Bcl6(+)cells are generated from highly proliferating CD62L(int)T cells and retain high proliferative potential, which contributes to replenishment of effector T cells within the tumor.