scRNAseq of Kaede red+ CD45+ cells from draining-lymph nodes of YUMMER1.7 tumors day 21 post implantation

We find that chronic antigen presentation in LNs by dendritic cells drives the local proliferation and transient residence of tumor-egressing T cells thereby inflating the LN stem-like population. Consequently, maintenance of stem-like T cells and ICB response depends on constitutive lymphatic transport, which sustains both effector egress and antigen presentation in the LN. Finally, we find that metastasis disrupts the stem-like LN niche in patients and impairs response to ICB in mice.

We, therefore, define a continuous, peripheral lymphatic circuit that recycles tumor-experienced effector T cells to fuel durable systemic anti-tumor immune responses, providing mechanistic insight into the enhanced efficacy of neoadjuvant immunotherapy and highlighting the importance of preserving lymphatic transport for optimal cancer immunotherapy outcomes.