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  MA06 - PDL1, TMB and DNA Repair (ID 903)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 13:30 - 15:00, Room 206 AC

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    MA06.03 - PD-1 and Id-1 Combined Blockade Impacts Tumor Growth and Survival Through PD-L1 Expression and Tumor Infiltration by Immune-Related Cells  (ID 14033)

    13:40 - 13:45  |  Author(s): Juan Jose Lasarte
    • Abstract
    • Presentation
    • Slides

    Background
    

    PD-1/PDL-1 inhibitors are approved in advanced non-small cell lung cancer (NSCLC). Long-term survival rates associated to PD-1/PDL-1 blockade have changed treatment paradigm. However, many patients do not benefit from PD-1/PDL-1 blockade. New therapeutic combinations are under investigation. Id1 is involved in proliferation, angiogenesis and immunosuppression. We described Id1 as an independent prognostic factor in NSCLC (Ponz-Sarvise, Clin Cancer Res 2011) and more recently showed Id1’s role in lung cancer metastasis (Castanon, Cancer Letters 2017). Here we test a combined therapeutic strategy targeting PD-1 and Id1 in a murine lung cancer model.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Three in vivo studies evaluated the impact of Id1 inhibition in tumor cells, tumor microenvironment and in both, on tumor volumes and mice survival. A syngeneic tumor model using C57BL/6 and Id1-/- Id3+/- mice was created by subcutaneous injection of Lewis Lung Carcinoma (3LL) cells and Id1 silenced 3LL (Id1Sh) cells. After injection, mice were treated with an anti-PD-1 (RMP-1-14) monoclonal antibody or PBS. Tumor volumes according to mice strain, Id1 status in tumor cells and treatment were quantified. Mice's survival was calculated in those groups. Tumor CD8+ and CD3+ TILs and CD68+ cells were quantified by specific immunostainings.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Id1 inhibition in the tumor environment and the injected tumor cells, combined with anti-PD-1 treatment, induced a significant tumor growth impairment (p < 0.0001) and increased survival (p = 0.0051). CD3+ and CD8+ TILs and tumor CD68 + cells were significantly higher in tumors from mice with the combined Id1-PD-1 blockade treated with the anti-PD-1 inhibitor compared to control animals suggesting that tumor increased immune-related cells infiltration exerts the effector phase of the antitumor immune response. Additionally, PD-L1 expression seemed to be higher when Id1 expression was absent in the immune microenvironment (p = 0.04). Additional data based on multiplexed immunohistochemistry results will be presented at the meeting.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Id1 and PD-1 combined blockade in our syngeneic murine lung cancer model significantly impaired tumor growth and increased survival. Increased tumor PD-L1 expression and CD3+ and CD8+ TILs and CD68+ cells may explain these findings.

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