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Kezhong Chen

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    Proffered Paper session I (ID 57)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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      69O - Comprehensive profiling of genomic and TCR repertoire in localized stage lung adenocarcinomas from a prospective cohort study (ID 264)

      16:30 - 18:15  |  Presenting Author(s): Kezhong Chen

      • Abstract
      • Presentation
      • Slides


      Recently, neoadjuvant targeted therapy and immunotherapy have presented a promising clinical effect for localized stage non-small cell lung cancer. However, the characteristics and relationship of genomic and immune profiling in surgical lung adenocarcinomas has been poorly delineated to date.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We prospectively enrolled 100 consecutive patients with pulmonary nodule who intended to undergo curative lung resection during June 2017 to July 2018 (NCT03320044). We investigated the TCR repertoire using next-generation deep sequencing of the complementarity determining region 3 (CDR3) of the TCR β chain in the tissue and WBC samples. Target-capture deep sequencing of 1021 genes was used to detect genomic variations in both tissue and paired plasma samples.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      EGFR (65.4%), TP53 (36.5%) and KRAS (11.5%) mutated most frequently. KRAS (84.6%) was enriched in mucinous adenocarcinoma. High invasive subtype and no ground-glass opacity status is more likely to be increasing tissue TMB (p = 0.0016, p = 0.0012), higher T-cell clonality (p = 0.05, p = 0.05), and more HLA-LOH event (p = 0.038, p = 0.035). A median of TNB was 2 neoantigens/Mb and showed positive relation with TMB (r = 0.97, p < 0.0001). EGFR-mutant co-occurring mutations were enriched TGF-beta, PI3K-Akt, hippo and Leukocyte trans-endothelial migration pathway (q < 0.05). Lower TCR clonality was shown in patients with EGFR mutation and co-occurring hippo or Leukocyte trans-endothelial migration pathway. Alterations in DNA damage response (DDR) pathways were observed in 15.8% patients, and these patients showed higher clonality (p = 0.03). 35.3%(24/68) ctDNA-positive were found in Stage I with a mean ctDNA abundance of 0.18% (ranged from 0.012 to 3.3%), which suggested the challenge of bTMB in biomarker study of early-stage LUAD. Analysis of TCR repertoire from available paired WBC showed no obvious characteristics.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      This is the first prospective study integrating the correlation of genomic alteration and T-cell receptor in localized surgical LUAD. Analysis of co-altered pathway of EGFR-mutant LUAD and immune microenviroment will provide a better understanding in choosing biomarkers and optimal benefit patients for neoadjuvant therapy.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification


      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Jun Wang.

      213f68309caaa4ccc14d5f99789640ad Funding

      National Natural Science Foundation of China (No.81602001).

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.


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