Aldehyde Dehydrogenase 1 (ALDH1) Is a Novel Marker for Tumor-Associated Macrophages and Dendritic Cells in Mature B-Cell Lymphomas
Vasiliki Leventaki, Kranthi Kunkalla, Yandog Liu, Changju Qu, Nitin K Agarwal, Jeffrey L Medeiros, Francisco Vega-Vazquez. UT MD Anderson Cancer Center, Houston, TX
Background: The enzyme aldehyde dehydrogenase 1 (ALDH1) has been identified in migratory dendritic cells (DCs) that represent one subset of the antigen presenting cells in innate immunity. Currently, there are no studies investigating the tumor-associated ALDH1 positive stromal cells in the tumor microenvironment of lymphoid malignancies.
Design: Immunohistochemical studies for ALDH1 were performed on paraffin sections from reactive lymph nodes and 74 B-cell lymphomas: 16 DLBCL, 11 CLL/SLL, 11 CHL, 10 FL, 8 MCL, 10 BL, and 8 MZL. The ALDH1 positive cells were counted in 10 consecutive high power fields (x1000). Double immunofluorescence on paraffin sections was performed with ALDH1 and one of the following antibodies: CD1a, CD21, CD68/PG-M1, CD103, CD123, CD163, CD205, S-100, and NOS2. Double immunohistochemical stain for ALDH1 and PAX5 was performed in a subset of lymphomas.
Results: Two populations of ALDH1 positive cells were identified: macrophages and migratory/tissue resident DCs. In reactive lymph nodes, ALDH1 positive cells were present inside sinuses, germinal centers and interfollicular areas. In B-cell lymphomas, ALDH1 positive cells were admixed within tumor cells and their number and distribution were highly variable. ALDH1 positive cells were most numerous in DLBCL (range: 45-187; mean: 91) and BL (range: 47-119; mean: 84). In DLBCL, ALDH1 positive cells were composed of a mixture of macrophages and DCs, but in BL they were mainly represented by tingible-body macrophages. In lower grade B-cell lymphomas (CLL/SLL, FL, MZL) and in MCL a lower number of ALDH1 positive cells was observed. In CHL, the number of ALDH1 positive cells in the pleomorphic inflammatory infiltrate showed variation, ranging from 24 to 98 (mean: 53). In both reactive lymph nodes and B-cell lymphomas, ALDH1 positive cells showed coexpression for CD68, a subset for CD163 (M2-like phenotype), and CD205, and were negative for the remaining of the antibodies. In reactive lymph nodes but not in DLBCLs, a subset of ALDH1 positive cells was positive for NOS2 (M1-like phenotype). The tumor cells were negative for ALDH1 expression.
Conclusions: ALDH1 is expressed in the macrophages and migratory/tissue-resident DCs (CD68+, CD163+, CD205+) in both reactive lymph node and B-cell lymphomas. High-grade B-cell lymphomas (DLBCL and BL) are characterized by the highest number of ALDH1 positive cells. ALDH1 positive cells in the tumor microenvironment may play a prominent function in immunologic tolerance and may represent a novel microenvironment-targeted molecule in B-cell lymphomas.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 236, Wednesday Afternoon