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M.C. Aubry



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    OA 13 - Immuno-Biology (ID 677)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      OA 13.07 - Contraction of T Cell Clonality in Lung Cancer Metastases (ID 7542)

      11:00 - 12:30  |  Author(s): M.C. Aubry

      • Abstract
      • Presentation
      • Slides

      Background:
      Clonal evolution and the heterogeneity of non-small cell lung cancer (NSCLC) may affect patient outcomes through variations in treatment planning, response to therapy, and drug resistance. Even less is known about the diversity of the adaptive immune response to primary and metastatic lesions in this disease. We sought to characterize the richness, abundance and overlap of T cell clones between paired primary NSCLC lesions and brain metastases.

      Method:
      We identified 20 patients with NSCLC with paired, fully resected primary lesions and brain metastases with sufficient tissue available in our clinical archives. DNA was purified from formalin-fixed paraffin-embedded specimens. The complementarity determining region 3 of T-cell receptor β was profiled by next generation sequencing to identify unique T cell clones. Sample richness (including iChao1 and Efron-Thisted Estimator), and clonal abundance (Simpson’s diversity index) were compared between paired lesions with the paired t test. Overlap in clonality was measured with the Morisita index.

      Result:
      There was a significant contraction of T cell clonality in paired metastases compared to primary lesions (mean of differences -2803, 95% CI -4202 to -1405; p=0.0005). The decreased richness in clonality in brain metastases was also supported by significant differences in iChao1 (mean of differences -20355, 95% CI -29561 to -11149; p=0.0002) and the Efron-Thisted Estimator (95% CI -21331 to -7216; p=0.0004). Simpson’s diversity index was higher in brain metastases than primary lesions (mean of differences 0.002, 95% CI 0.001 to 0.004; p=0.05), but low overall. Only a fraction of T cell clones in primary lesions were also found in brain metastases (mean Morisita Index 0.23).

      Conclusion:
      There is greater richness but less abundance of T cell clones in primary NSCLC lesions compared to paired brain metastases. Although the blood brain barrier may restrict T cell trafficking to tumors, the minimal overlap in T cell clones may reflect the genetic divergence of metastatic tumor clones.

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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-016 - Comparison of PD-L1 Immunohistochemical Staining between EBUS-TBNA and Resected Non-Small Cell Lung Cancer Specimens (ID 8964)

      09:30 - 16:00  |  Author(s): M.C. Aubry

      • Abstract

      Background:
      PD-L1 can be detected by immunohistochemical (IHC) analysis and has emerged as a biomarker that predicts which patients are more likely to respond to anti-PD-L1/PD-1 immunotherapies in non-small cell lung cancer (NSCLC)(1, 2). To date, there is no evidence to support or refute PD-L1 IHC staining on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples. Our study aimed to establish the sensitivity, specificity, positive predictive value, and negative predictive value of PD-L1 IHC staining reliability on EBUS-TBNA samples, when compared to resected tumor specimens.

      Method:
      A retrospective review was performed on all patients who underwent an EBUS-TBNA of either a lymph node(s) or the tumor itself, who subsequently had surgical resection of their tumor between July 2006 through September 2016. Patients who had a concordant NSCLC EBUS-TBNA diagnosis with their resected tumor were included. Patients with small cell lung cancer were excluded. All EBUS-TBNA samples were obtained using Olympus EBUS bronchoscopes and a 22-gauge ViziShot needle (Olympus Medical Systems Corp., Tokyo, Japan). The Dako PD-L1 IHC 22C3 (Agilent Pathology Solutions) assay was used. A positive PD-L1 stain was defined as ≥1% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

      Result:
      We performed 5448 EBUS-TBNA procedures for lung cancer. Seventy patients were included in our analysis. To date, 23 cases have been stained and reviewed (Table). The sensitivity and specificity was 71% and 100%, respectively. The PPV and NPV were 100% and 69%, respectively. We expect to complete our analysis of all patients prior to the IASLC World Conference.

      Comparison of PD-L1 IHC stain between EBUS-TBNA samples and resected tumor specimen.
      Resected tumor PD-L1 positive Resected tumor PD-L1 negative
      EBUS-TBNA PD-L1 positive 10 0
      EBUS-TBNA PD-L1 negative 4 9


      Conclusion:
      Positive PD-L1 IHC staining on EBUS-TBNA aspirates appears to have a strong correlation with resected tumor specimen. When EBUS-TBNA aspirates are negative for PD-L1 staining, additional tumor specimens are required to confirm the PD-L1 status.