Immune Infiltration and Melanoma Target Antigen Expression in Lymphangioleiomyomatosis (LAM)
J Klarquist, M Picken, R Love, D Dilling, IC LePoole. Loyola University Medical Ctr, Maywood
Background: LAM belongs to PECOMAs, tumors showing perivascular epithelioid cell differentiation, which co-express myoid and melanocytic markers and show marked female predominance. Although PECOMAs elsewhere in the body are mostly benign, LAM relentlesly progresses to pulmonary failure. Several melanocytic markers may be expressed by LAM including: HMB-45, which is reactive with melanoma-associated antigen gp100 and MART-1. In melanoma and vitilligo, infitrating T cells have been shown to target both gp100 and MART-1 and this may be associated with depigmentation and tumor regression. Lungs affected by LAM are also frequently infiltrated by immune cells; however, there is a paucity of data regarding their role in LAM and levels of expression of various melanocytic markers.
Design: We performed immunohistochemical (IHC) and FACS analysis of lung tissue from 5 LAM patients, 3 controls and 3 melanoma tumors. Melanoma markers (HMB-45, MART-1, tyrosinase, TRP-1 and TRP-2) were tested by IHC and their expression was measured semi-quantitatively. Infiltrating immune cells were counted by cell sorting using FACScanto and tested with T cell (CD4 and CD8), dendritic and macrophage markers and were semi-quantified. LAM was compared to normal lung and melanoma.
Results: Expression of gp100, MART-1, TRP-1 and TRP-2, but not tyrosinase, was detected in LAM. Expression of TRP-1 was more prominent than gp100 in LAM and more prominent than in melanoma, while TRP-2 was comparable in both. In LAM, partially overlapping subsets of cells expressed gp100 and MART-1. T cell density in LAM and normal lung (4% of sorted cells) was similar but it was reduced compared to melanoma. Cd11c+ dendritic cells in LAM were 50% more abundant than in normal lung but 50% less than in melanoma. Macrophages were much more abundant in LAM than in control lung and comparable to melanoma tumors. The differences in T cell density between LAM and melanoma were primarily due to more abundant CD8+ T cell infiltration in melanoma.
Conclusions: These data suggest that infiltrating lymphocytes may be involved in the immune targeting of LAM cells, and that this targeting extends beyond antigens detectable by HMB-45 stain. The infiltrating immune cells in LAM may specifically target gp100 and MART-1, the same antigens that are targeted in melanoma. Further testing of the cytotoxic potential of the infiltrating immune cells in LAM is needed in order to explore the possibility of therapeutic immune modulation in LAM and the feasibility of using anti-melanoma vaccines for the treatment of LAM.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 259, Tuesday Afternoon