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Josette William



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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-42 - Using a Multiplexed Immunofluorescence Approach to Compare Immune Cell Populations in Subtypes of Non-Small Cell Lung Cancer (Now Available) (ID 1464)

      08:00 - 18:00  |  Author(s): Josette William

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases, and is characterized by a poor response to chemotherapy and a low survival rate. Treatment targeting the immune checkpoint inhibitor pathway PD-1/PD-L1 has been found to be effective against NSCLC with manageable side effects, but with only 20-25% of patients showing a positive response there is an urgent need for additional immunotherapy options for this group of patients.

      NSCLC is a very heterogeneous disease with the two most common types being adenocarcinoma (ADCA) accounting for about 70% of all NSCLC cases, and squamous cell carcinoma (SCC) accounting for about 20% of all cases. In a study profiling the molecular signatures of these two NSCLC subtypes the existence of specific molecular networks and subtype-specific differences was reported (1), while a study using flow cytometry to analyze NSCLC on protein level reported the immune cell composition to be fundamentally different in ADCA compared with SCC (2). However, to the best of our knowledge this study is the first of its kind performing an extensive analysis of NSCLS immune cell composition in tissue.

      1. Kargl et al. Nature Commun, 2017 Feb 1;8.

      2. Daraselia et al. Am J Cancer Res, 2012 2(1).

      Method

      In order to perform a comprehensive immunoprofiling of ADCA and SCC we used MultiOmyx™, an immunofluorescence (IF) multiplexing assay that utilize a pair of directly conjugated Cyanine dye-labeled (Cy3, Cy5) antibodies per round of staining. Using a 16-marker panel we have analyzed the proportion of B cells, T cell subtypes, M1/M2-type tumor-associated macrophages, as well as the expression of not only PD-1 and PD-L1, but also of more novel immunotherapy targets LAG-3, TIM-3, ICOS, and OX40 in 20 samples from patients with NSCLC (10 ADCA and 10 SCC).

      Result

      While we found LAG-3 expressed mainly on T cytotoxic cells in both subtypes, the overall density of LAG-3 was increased from 130 cells/mm2 in ADCA to 239 cells/mm2 in SCC. Likewise, we found the density of TIM-3 to be increased from 413 cells/mm2 in ADCA to 1100 cells/mm2 in SCC, while the density of PD-L1 was decreased from 1626 cells/mm2 in ADCA to 1089 cells/mm2 in SCC.

      Conclusion

      It is our hope that these data will help provide new insights into the biology of ADCA and SCC that can ultimately be used to explore novel immunotherapeutic interventions for lung cancer treatment.

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