Associate Professor Concordia University Mequon, Wisconsin, United States
Disclosure(s):
Jessica Loppnow: No financial relationships to disclose
Introduction/Rationale: Infiltrating regulatory T cells (Tregs) within tumor microenvironments suppress tumor immune responses and are correlated with increased tumor growth. However, the mechanisms regulating distribution of Tregs within tumors or nearby tumor-draining lymph nodes (dLN) is not fully understood. During lymphocyte trafficking, L-selectin functions to regulate migration of lymphocytes to lymph nodes through high endothelial venules (HEV). L-selectin can also mediate lymphocyte trafficking to sites of inflammation by binding to ligands present on inflamed endothelium.
Methods: Using a murine 4T1 breast cancer model in L-selectin deficient mice (Foxp3EGFP/L-selectin-/- ), Treg cell migration to tumors, draining and non-draining lymphoid tissue during tumor progression was tracked and quantified by flow cytometry.
Results: Here we demonstrated L-selectin facilitates Treg cell distribution and migration within secondary lymphoid and 4T1 tumor tissue. Treg populations preferentially accumulated in tumor dLNs and increased at higher rates than conventional CD4+ T cell populations during tumor progression. L-selectin deficient mice (Foxp3EGFP/L-selectin-/- ) had significantly reduced numbers of Treg populations within the dLN, ndLN and within tumor tissue. Migration of Tregs into dLNs occurred primarily from the blood through HEV and was L-selectin-dependent. However, Treg cells were also able to enter dLNs from the tumor through afferent lymphatics. In L-selectin deficient mice, Treg cell migration into solid tumor tissue was also reduced during late stage tumors.
Conclusion: Therefore, these studies demonstrate Treg influx into tumor and dLNs occurs by specific homing of Tregs to these tissues and may be dependent on Treg expression of L-selectin.
