(1) Kahn BM (2) Ng RWS (3) Kim IK (4) Eskandarian C (5) Chen CO (6) Huang B (7) Lucas A (8) Li L (9) Maillard I (10) Stanger BZ
(1) Kahn BM (2) Ng RWS (3) Kim IK (4) Eskandarian C (5) Chen CO (6) Huang B (7) Lucas A (8) Li L (9) Maillard I (10) Stanger BZ
Lymph nodes (LNs) are the staging grounds for anti-tumor immunity, therefore their high susceptibility to metastatic colonization is a paradox. Previous studies have suggested that extrinsic tumor-derived factors precondition the draining LN to enable tumor cell survival by promoting a state of immune suppression. Here, we investigate whether properties of the LN itself may impede its ability to clear metastasizing tumor cells. Using multiple immunocompetent transplant models, we show that LNs possess intrinsic features, independent of preconditioning, which make them an advantageous site for tumor cells to evade T cell control. Tumor growth in the LN is facilitated by regulatory T cells, which locally suppress the cytolytic capacity of tumor-specific CD8 T cells by restricting IL-2. These findings identify an intrinsic mechanism that contributes to the high rate of LN metastasis in solid tumors.
Author Info: (1) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (2) Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States. (3) University
Author Info: (1) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (2) Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States. (3) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (4) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (5) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (6) Qilu Hospital of Shandong University, Jinan, China. (7) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (8) Huazhong University of Science and Technology, Wuhan, China. (9) Memorial Sloan Kettering Cancer Center, New York, NY, United States. (10) University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Citation: Cancer Discov 2025 Apr 24 Epub04/24/2025
