Session: 622. Lymphoma Biology—Non-Genetic Studies: Poster III
Hematology Disease Topics & Pathways:
Diseases, Hodgkin Lymphoma, Biological Processes, Technology and Procedures, Clinically relevant, Lymphoid Malignancies, imaging, immune mechanism, proteomics
Herein, we report an analysis of MDSCs and ‘protumoral’ M2 macrophages using MultiOmyx hyperplexed immunofluorescence (IF) assay in 9 clinical samples diagnosed with HL. MultiOmyx is a proprietary multi ‘omic’ technology that enables detection and visualization of up to 60 biomarkers on a single 4µM FFPE slide (Gerdes MJ. et al. PNAS 2013). The HL FFPE sections were stained with a 13-marker panel including Arginase 1, CD11b, CD14, CD15, CD16, CD33, CD68, CD163, HLA-DR, CD3, CD4, CD8 and FOXP3. We observed that both M-MDSC (Fig 1A, characterized as CD11b+CD14+CD15-CD33+HLA-DR-) and G-MDSC (Fig 1B, identified as CD11b+CD14-CD15+CD33+HLA-DR-) accumulated within the TME in all 9 HL samples, with higher frequency of G-MDSCs over M-MDSCs. Arg1 expression was detected exclusively in G-MDSC population (Fig 1C). The data also revealed an abundant M2 macrophages (Fig 1D, characterized as CD68+CD163+) present in all HL samples. The detection of both MDSCs and M2 macrophages in HL samples supports the hypothesis that these cells contribute to the establishment of an immunosuppressive TME. Using the MultiOmyx proprietary algorithm, which takes into account the staining patterns, we will next quantify the counts and density of different tumor-resident myeloid subsets and measure the spatial distance between each subset of tumor-resident myeloid cells to the neoplastic Reed-Sternberg cells. Correlation study will also be performed to determine if significant correlations exist between MDSCs and TAMs and how these immunosuppressive myeloid cells are related to the Regulatory T cells (CD3+CD4+FOXP3+) in HL samples. In addition to HL samples, the same 13-plexed panel will be utilized to characterize the myeloid cell population from AML patients.
TAMs and MDSCs are emerging as potential biomarkers for diagnosis and prognosis of cancer as well as therapeutic targets. The comprehensive myeloid cells phenotyping offered by MultiOmyx 13-plexed panel has the potential to monitor the changes of immunosuppressive myeloid cells in response to immune modulating drugs such as MDSC-targeting drugs (e.g. PDE-5 inhibitors, COX-2 inhibitors), TAM-targeting agents (e.g. anti-CSF1R) and combined therapy in treatment of lymphoma and leukemia.
Disclosures: No relevant conflicts of interest to declare.
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