Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8(+) T cells in lymph nodes
- Author(s)
- Lai, J; Chan, CW; Armitage, JD; Audsley, KM; Huang, YK; Derrick, EB; Carstensen, LS; Scheffler, CM; Jones, ME; Sek, K; Principe, N; Kim, JS; House, IG; Chen, AXY; Yap, KM; Middelburg, J; Munoz, I; Nguyen, D; Tong, J; Hoang, TX; Todd, KL; Evrard, M; Chee, J; Mackay, LK; Forrest, ARR; Parish, IA; Bosco, A; Waithman, J; Beavis, PA; Darcy, PK;
- Journal Title
- Nature Immunology
- Publication Type
- Online publication before print
- Abstract
- Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (T(PEX)), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. Here we show that treatment with Fms-related tyrosine kinase 3 ligand (Flt3L) expands CD62L(+)SLAMF6(+)CD8(+) T cells in the tumor through a mechanism that requires XCR1(+) dendritic cells to traffic to the tumor-draining lymph node. The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8(+) T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8(+) T cells within tumors through a mechanism that is dependent on lymph node egress.
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41590-026-02419-4
- Open Access at Publisher's Site
https://doi.org/10.1038/s41590-026-02419-4- Terms of Use/Rights Notice
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Creation Date: 2026-02-24 05:56:04
Last Modified: 2026-02-24 05:56:10