Pulmonary lymphangioleiomyomatosis (LAM) is a devastating progressive disease primarily affecting women of childbearing age. In LAM patients, abnormal muscle-like cells begin to grow out of control in certain organs or tissues, especially the lungs, lymph nodes, and kidneys. Two hallmarks of LAM are expanded lymphatic vessels and an immunosuppressive microenvironment in the lungs. We will determine the effects of LAM cells on lymphatic functions, and therapeutic efficacy of immunotherapies used in combination with rapamycin, the only FDA-approved LAM treatment. This work will bring novel insights into effects of LAM on lymphatic functions and may provide new avenues for LAM treatments.
Our findings from year 1 have demonstrated that LAM suppresses immune activation in the lungs, and that therapeutic immune activation in LAM can be achieved using treatments that activate toll-like receptors on antigen presenting cells — the “gatekeepers” of the immune system that protect the body from invading bacteria, viruses and other microorganisms.