Author of

• 25789

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  MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Treatment of Locoregional Disease - NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 13:30 - 15:00, Room 105

  • 25792

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    MA05.03 - Immune Microenvironment and its Association with Adjuvant Chemotherapy Benefit in Locoregionally Advanced Lung Adenocarcinoma (ID 12999)

    13:40 - 13:45  |  Presenting Author(s): Raj Ghanshyam Vaghjiani
    • Abstract
    • Presentation
    • Slides

    Background
    

    The impact of the tumor immune microenvironment on the effectiveness of platinum-based adjuvant chemotherapy (ACT) in locoregionally advanced (stage II-III) lung adenocarcinoma (ADC) is unknown. We performed an analysis of the cellular components of the tumoral and tumor-associated stromal immune environment in stage II-III lung ADC and examined their association with ACT benefit.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Tissue microarrays (6 tumor and 3 stromal cores from each tumor) were constructed using resected tissue from patients with pT2-T4N1 lung ADC (n=500, 2000-2012) who did (n=225) and did not (n=214) receive ACT. Multiplex immunofluorescence was used to determine the quantity, localization, and colocalization of 21 types of immune cells and markers (including PD-1, PD-L1, CD3, CD20, CD68, CD163, MPO, and PanCK). The association between immune cell infiltration and recurrence free probability (RFP) was compared using Kaplan-Meier methods, and benefit from ACT by unsupervised hierarchical cluster modeling.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Overall, increased tumoral infiltration of CD20⁺ B-cells and CD3⁺ and CD4⁺ T-cells was associated with an improvement in 5-yr RFP (CD20⁺ low vs high: 37% vs 49%, p=.03; CD3⁺: 39% vs 48%, p=.003; and CD4⁺: 39% vs 47%, p=.02, respectively) whereas increased stromal MPO⁺ neutrophil infiltration was associated with a worse 5-yr RFP (low vs high: 50% vs 38%, p=.003). Among patients who received ACT, cluster modeling revealed 5 risk groups (Groups A-E; Figure) with immune signatures including tumoral B-cells and CD163⁺PD-1⁺ macrophages as well as stromal CD57⁺ NK-cells and CD163⁺PD-L1⁺ macrophages that provided a progressive stratification of RFP following adjuvant treatment.

    

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Immune infiltration analysis can predict benefit from ACT and thereby provide a rationale to select patients for either chemotherapy, immunotherapy, or combination therapy following surgical resection.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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