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Roy S. Herbst



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    MS21 - Giants in Thoracic Oncology (ID 869)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 17:00, Room 105
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      MS21.06 - Immunotherapy - Sequence or Combination? (Now Available) (ID 13379)

      16:05 - 16:15  |  Presenting Author(s): Roy S. Herbst

      • Abstract
      • Presentation
      • Slides

      Abstract

      Despite advances in the treatment of cancer, with novel molecularly targeted therapies and drug combinations, lung cancer continues to be one of the leading causes of cancer death worldwide. For this reason, significant efforts have been made to examine the interaction between cancer and the immune system. This has led to the discovery of the programmed death 1 (PD1) and ligand (PDL1) pathway, which was found to play a key role in immune evasion by cancer cells and the formation of a tumor microenvironment. Blockade of this pathway enables the ability of the innate immune system to activate their anticancer responses and to reverse the tumor microenvironment. Newly approved drugs, such as nivolumab and pembrolizumab, have mechanisms of action that inhibit PD1, while others like atezolizumab, block PDL1. Although, responses with these drugs have shown significant activity in some patients, only 20-30% of patients respond overall. In this talk, mechanistic studies to identify predictive markers of response will be discussed along with markers of resistance (both primary and acquired). In addition, novel combinations of immunotherapy with chemotherapy, targeted therapy and even chemotherapy will be explored including their use in sequence or combination.

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-20 - Immunologic Characterization of Fibrinous Pericarditis as an Immune Checkpoint Blockade Toxicity in NSCLC (ID 14058)

      16:45 - 18:00  |  Author(s): Roy S. Herbst

      • Abstract

      Background

      Immune checkpoint inhibitors have revolutionized the treatment paradigm in number of cancers including Non-Small Cell Lung Cancer (NSCLC) but unrestrained modulation of the immune system remains a challenge. Here, we characterized the immune infiltration in the toxicity site and compared immune profile in primary tumor in three patients treated with PD-1/PD-L1 axis inhibitors and developed fibrinous pericarditis (FP)

      Method

      We used the AQUA method of quantitative immunofluorescence (QIF) to assess multiplexed panels identifying immune cell populations and their activation status in pre-treatment, post-treatment primary tumor, post-treatment metastatic tumor and the toxicity sites (including pericardial tissue) from 3 NSCLC patients. We also compared the expression of 730 immune-related genes across sites from the 3 patients with FP and 2 NSCLC patients with different toxicity sites after immunotherapy (hypophysitis and myocarditis) using Nanostring Sprint platform.

      Result

      In immune infiltration assessment, TILs markers’ expression (CD4, CD8 and CD20) did not differ between primary tumor and toxicity site. There was a trend towards higher CD3+ expression in the toxicity samples but T-cell activation markers expression, Granzyme B and Ki67, was significantly lower in the pericarditis samples. Interestingly, high Granzyme B expression in CD3- cells and CD56+ cells were seen in the pericarditis samples. CD68+ expression, as well as PD-L1 expression in macrophages, was significantly higher (p<0.0001) in the pericarditis samples. mRNA analysis confirmed the QIF findings, with the chemokine profile indicating an M1 macrophage polarization. Additionally, there was a trend towards higher NCR1, perforin1 and Granzyme B gene expression in the toxicity samples, further supporting a possible role of Natural Killer (NK) cells in the development of toxicity.

      Conclusion

      Our findings suggest that macrophages and possibly NK cells contribute to inflammatory tissue damage in immune related adverse events. Conversely, T-cells that were infiltrating the toxicity sites had low expression of activation markers, further indicating that toxicity may be mediated by other cellular pathways.

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    YI01 - Young Investigators Session (ID 988)

    • Event: WCLC 2018
    • Type: Young Investigator Session
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/23/2018, 08:00 - 11:30, Room 106
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      YI01.02 - Planning a Career in Lung Cancer - Clinical Trials (Now Available) (ID 14671)

      08:10 - 08:20  |  Presenting Author(s): Roy S. Herbst

      • Abstract
      • Presentation

      Abstract not provided

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