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Updated: Aug 14, 2026
Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis
Published on: January 26, 2024
Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment
Shihao Chen1, Hiroto Kawashima, John B Lowe
1Glycobiology Program, Cancer Research Center, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Abstract:
Natural killer (NK) cells are known to reject certain tumors in vivo; however, the ability of NK cells to prevent metastasis of tumors into secondary lymphoid organs has not been addressed. Here, we report that in tumor-bearing hosts, NK cells are recruited to regional lymph nodes in wild-type mice, but not in mice deficient for L-selectin or L-selectin ligands. By adoptive transfer and complete Freund's adjuvant stimulation experiments, we demonstrated that L-selectin on NK cells and L-selectin ligands on endothelial cells are essential for NK cell recruitment to lymph nodes. Furthermore, freshly isolated resident lymph node NK cells lysed tumors efficiently, and metastasis of B16 melanoma cells to draining lymph nodes was suppressed in wild-type or Rag-1-deficient mice, but not when NK cells were depleted. Although L-selectin-deficient NK cells efficiently lysed tumor cells in vitro, NK cell-dependent suppression of tumor metastasis was diminished in mice deficient for L-selectin or L-selectin ligands because of insufficient NK cell recruitment to lymph nodes. Moreover, tumor metastasis was substantially inhibited in L-selectin-deficient mice reconstituted with wild-type NK cells. These findings indicate that L-selectin-mediated NK cell recruitment plays a crucial role in the control of tumor metastasis into secondary lymphoid organs.
Insights
Natural killer (NK) cells prevent tumor metastasis to lymph nodes. L-selectin mediates NK cell recruitment to lymph nodes, which is crucial for controlling cancer spread.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Trafficking
Background:
- Natural killer (NK) cells are recognized for their role in rejecting tumors.
- The capacity of NK cells to inhibit tumor metastasis to secondary lymphoid organs remains largely unexplored.
Purpose of the Study:
- To investigate the role of NK cells in preventing tumor metastasis to lymph nodes.
- To determine the mechanisms underlying NK cell recruitment to lymph nodes in the context of cancer.
Main Methods:
- Utilized wild-type and genetically modified mice (deficient for L-selectin or L-selectin ligands).
- Employed adoptive transfer experiments and complete Freund's adjuvant stimulation.
- Assessed NK cell recruitment to lymph nodes and tumor metastasis using B16 melanoma models.
- Evaluated tumor cell lysis in vitro and in vivo.
Main Results:
- NK cell recruitment to regional lymph nodes was dependent on L-selectin and its ligands.
- Resident lymph node NK cells demonstrated efficient tumor cell lysis.
- Tumor metastasis to draining lymph nodes was suppressed in wild-type mice but not in NK cell-depleted or L-selectin-deficient settings.
- L-selectin-deficient NK cells showed impaired metastasis control due to reduced lymph node homing.
Conclusions:
- L-selectin-mediated NK cell recruitment is essential for controlling tumor metastasis to secondary lymphoid organs.
- This pathway highlights a critical mechanism for immune surveillance against cancer spread.
