The lymphatic system is responsible for delivery of fluid and small molecules from tissues to the
lymph node (LN), where immune system surveillance of self and foreign antigens occurs.
Growth of LN lymphatic sinuses is a feature of multiple diseases including cancer, arthritis, and
inflammation. Recent studies have suggested an important role for LN lymphatic sinuses in the
orchestration of the immune response, and for the reinforcement of peripheral tolerance
within the LN. Lymphatic vessels are a major route of tumor dissemination, with the tumor
draining LN being the first site of metastasis in many cancers. We have identified a 10.1.1
monoclonal antibody that recognizes the lymphatic sinus-specific surface protein, mCLCA1,
which binds to LFA-1 on lymphocytes to mediate lymphatic sinus/lymphocyte interaction.
Interaction of lymphocytes with lymphatic sinuses has been shown to promote lymphocyte
survival. We propose to use this monoclonal antibody and mCLCA1-deficient mice to study
lymphatic endothelial cell (LEC)/lymphocyte interactions and regulation of lymphocyte survival
in vivo. Understanding how LECs regulate lymphocyte survival within the LN could be important
for developing targeted immunotherapies for cancer. Manipulation of lymphocyte survival
could be beneficial to promoting a productive anti-tumor immune response.