Role of Proinflammatory Cytokines in Thermal Activation of Lymphocyte Recruitment to Breast Tumor Microvessels
Abstract
The tumor microvasculature is a barrier to immunotherapy because of its failure to express adhesion molecules necessary for recruitment of tumor-reactive lymphocytes. Immune cells are frequently excluded from the intratumoral region of primary tumors including breast cancer. Our studies demonstrate that fever-range thermal therapy increases lymphocyte trafficking selectively in tumor sites and secondary lymphoid organs, but not in extralymphoid organs. Intravital microscopy studies and short term homing assays allow us to observe thermal enhanced lymphocyte-endothelial interactions in vivo. Underlying mechanism was detected focusing on the trafficking molecules which control egress of blood-borne lymphocytes into tissues. Heat treatment enhanced intravascular expression of intercellular adhesion molecule-1 (ICAM-1) in tumor microvessels and high endothelial venules in lymphoid organs. This induced ICAM-1 expression is functional linked with thermal activated lymphocyte-endothelial interaction and lymphocyte homing. Neutralization of proinflammatory cytokines IL-6, but not TNF or IL-1 beta, suppresses thermal induction of ICAM-1-dependent lymphocyte recruitment. Soluble gp130 also prevented ICAM-1 induction, indicating that thermal activities in vascular targets are dependent on an IL-6 trans-signaling mechanism. These results support the hypothesis that IL-6-dependent signaling mechanisms activate tumor immunity through stimulation of heightened trafficking of lymphocyte subsets to tumor sites and lymphoid organs during fever-range thermal therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469221
Entities
People
- Chen Qing
Organizations
- Health Research, Incorporated