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Raj Ghanshyam Vaghjiani

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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
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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


      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.


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