Expansion and mobilization of virus-specific stem-like CD8 T cells in chronic viral infection after treatment with a long-acting IL-7, NT-I7.

PD-1TCF1 stem-like CD8 T cells are a progenitor population that provides a proliferative burst of effector CD8 T cells upon PD-1 blockade therapy, making them a key therapeutic target in antiviral and anticancer immunotherapy. Here, we show that IL-7 therapy preferentially expands these stem-like CD8 T cells, using NT-I7, a long-acting Fc-fused recombinant human IL-7 (efineptakin alfa). Gene profile analysis showed that a proliferating stem-like cluster induced by NT-I7 exhibited enrichment of genes related to lymphocyte migration. After NT-I7 treatment, proliferation of stem-like cells in the spleen was initiated within the white pulp, followed by egress into the red pulp. NT-I7 treatment led to an increase in stem-like CD8 T cells in circulation and peripheral tissues, contrasting with their resident property in lymphoid organs. These findings suggest NT-I7 as a promising strategy to expand and mobilize stem-like CD8 T cells to enhance antiviral and anticancer immunotherapies.