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H. Dong



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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): H. Dong

      • 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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