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M. Karlsson



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    MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 05.13 - Scavenger Receptor MARCO Defines a Targetable Tumor-Associated Macrophage Subset in Lung Cancer (ID 8641)

      15:45 - 17:30  |  Author(s): M. Karlsson

      • Abstract
      • Presentation
      • Slides

      Background:
      Tumor-associated macrophages (TAMs) with immunosuppressive and tumor promoting features are attractive targets for immunotherapy. MARCO is a scavenger receptor expressed on a subpopulation of macrophages in secondary lymphoid organs. A recent study performed in animal models concluded that treatment with an anti-MARCO antibody results in reprogramming of the TAMs and inhibition of tumor growth and metastatic spread. The expression and function of MARCO in lung cancer TAMs is not known.

      Method:
      The infiltration of TAMs expressing MARCO, CD68, CD163 and MSR1, in the tumor and stromal compartments, was analyzed by immunohistochemistry in a non-small cell lung cancer (NSCLC) cohort (n=352). In addition, PD-L1 expression was assessed on tumor cells. Immunofluorescence was performed on selected cases to evaluate marker co-expression. Associations to immune cells and regulatory inflammatory pathways were studied in a subset of cases (n=174) with available RNA-seq data.

      Result:
      A large variance in TAM density could be observed between cases as well as a strong correlation between CD68 and CD163, indicating a pro-tumor phenotype of infiltrating macrophages. Correlation to clinical data showed a trend towards worse survival for patients with high macrophage infiltration. TAM expression of MARCO was seen on a subpopulation of pro-tumor macrophages. The majority of MARCO expressing TAMs were found to be located within tumor cell nests. Interestingly, stromal macrophages expressing MARCO tended to aggregate in close proximity to the tumor nests. On the transcriptomic level, increased MARCO gene expression correlated to genes linked to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules like PD-L1 and CTLA-4. The association between macrophage infiltration and tumor cell PD-L1 expression was confirmed by immunohistochemistry. Also, co-expression of PD-L1 and MARCO could be detected on certain macrophages within the tumor cell nests.

      Conclusion:
      MARCO expression characterizes a specific subpopulation of pro-tumor macrophages that are enriched in PD-L1 positive NSCLC cases. Patients with significant infiltration of MARCO positive TAMs could benefit from treatment with anti-MARCO antibodies, possibly in combination with available immune checkpoint inhibitors.

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