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Lymphatic egress recycles tumor-experienced effector CD8 T cells to sustain immune surveillance

Delclaux, I.; Ventre, K. S.; Besson, N. R.; Muijlwijk, T.; Ibrahim, M.; Wang, G.; Heim, T. A.; Steele, M.; Huang, A. C.; Schober, M.; Osman, I.; Lund, A. W.

2026-05-05 immunology
10.64898/2026.04.30.721705 bioRxiv
Show abstract

Successful anti-tumor immune surveillance depends on stem-like CD8+ T cells that are enriched in tumor-draining lymph nodes (LN), but how they are maintained over time remains poorly understood. Here, we identify a continuous lymphatic circuit that sustains stem-like CD8+ T cells. Using photoconversion to fate-map intratumoral T cells we demonstrate that effector cells exit the tumor microenvironment and migrate back to the draining LN. These tumor-specific, migratory effector T cells avoid chronic antigen stimulation, re-express the transcription factor associated with self-renewal, TCF1, and enter a stem-like state in the LN. Antigen presentation in LNs by dendritic cells drives their proliferation thereby inflating the LN stem-like population. Consequently, maintenance of stem-like T cells and ICB response depends on constitutive lymphatic transport, while LN metastasis compromises the stem-like niche, diminishing ICB response. We, therefore, define a continuous, peripheral lymphatic circuit that recycles tumor-experienced effector T cells to fuel durable, systemic immune surveillance.

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