Pre-existing intratumoral stem-like CD8⁺ T cells drive radiotherapy-induced tumor immunity

CD8⁺ T cells are crucial for both spontaneous and therapy-induced restriction of tumor progression. Although many patients with cancer undergo radiotherapy, the precise effect of this genotoxic treatment on tumor-associated CD8⁺ T cells is insufficiently understood. Here, we investigated the influence of radiotherapy on intratumoral CD8⁺ T cells. We found that, although these CD8⁺ T cells initially decline following radiotherapy, they subsequently expand and are both essential and sufficient for early tumor control. In response to radiotherapy, stem-like CD8⁺ T cells proliferate and differentiate into effector CD8⁺ T cells, making them key drivers of tumor immunity. Our findings underscore the pivotal role of intratumoral stem-like CD8⁺ T cells in mediating radiotherapy-induced anti-tumor immunity and provide deeper insights into the dynamic behavior of CD8⁺ T cells during tumor control after radiotherapy.