In the face of tumour and viral challenges, TCF1+PD1+ stem-like T cells (TSL cells) are a crucial CD8+ T cell subset capable of self-renewal and of replenishing cytotoxic effector T cells. Crucially, TSL cell populations expand upon immune checkpoint blockade, thus potentiating the therapeutic recovery of antitumour T cell responses. In a recent preprint (not peer reviewed), Hor et al. interrogate TSL cell niches in tumour-draining lymph nodes (tDLNs). They define a SLAMF6+ TSL cell subset with high T cell receptor (TCR) affinity, maintenance of which is regulated by PD1 signalling and prolonged association with conventional type 1 dendritic cells (cDC1s).

The authors used 3D multiplex immunofluorescence imaging in optically cleared tDLNs of mice bearing subcutaneous KP-OVA tumours, enabling the spatial and functional profiling of tumour-targeting CD8+ T cells. An XCR1 fluorescent reporter mouse model enabled the additional visualization of XCR1+ cDC1s.