Overcoming obstacles to naive T lymphocyte trafficking in tumor-draining lymph nodes

Results: Compared to resting LN, lymphocyte entry into TdLN was diminished by ~50%, suggesting a localized mechanism of tumor immune escape. Intravital microscopy revealed that while normal proportions of lymphocytes initiated tethering and rolling in high endothelial venules (HEV) of TdLN (34%), the fraction of lymphocytes that then transitioned to firm arrest was reduced compared to unchallenged lymph nodes (8 and 20%, respectively). Diminished trafficking in TdLN was attributed to suboptimal presentation of the CCL21 chemokine in HEV. We further determined that inflammatory cues triggered by systemic thermal therapy (STT, 39.5 ± 0.5°C, 6 h) restored normal T cell entry into TdLN, paralleling our previous findings in non-tumor–challenged mice. Improved homing was due to a reduction in rolling velocity and an increase in proportion of T cells undergoing firm arrest. STT was further shown to enhance the display of trafficking molecules required for firm arrest, i.e., CCL21 and ICAM-1 in HEV.