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  P2.02 - Biology/Pathology (ID 616)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23239

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    P2.02-041 - Update on Prospective Immunogenomic Profiling of Non-Small Cell Lung Cancer (ICON Project) (ID 10156)

    09:30 - 09:30  |  Author(s): I.P. Icon Team
    • Abstract
    • Slides

    Background:
    Given the rapidly changing therapeutic landscape for non-small cell lung cancer (NSCLC), a thorough understanding of the tumor immune environment is critical to the appropriate selection of patients and testing of immuno-oncology agents. We established a project aimed at defining the comprehensive and integrated immunogenomic landscape in NSCLC, including immune, genomic and clinical data from 100 surgically resected lung cancers.
    
    Method:
    Tissue samples were collected at the time of surgery, and blood samples before and after surgery up to 1-year. Tissue samples were subjected to tumor infiltrating lymphocyte (TIL) isolation and expansion; generation of PDX models,WES and in-silico neoantigen prediction, RNA sequencing, RPPA, CyTOF, T cell receptor sequencing, and multiplex immunofluorescence evaluation of immune cells and markers. Blood samples were processed for cfDNA, microRNA, and cytokine profiling.
    
    Result:
    93 out of 131 enrolled patients with median age 67 years contributed samples to ICON; 44% males, 80% former smokers, 12% never smokers. Majority had adenocarcinoma (60%) and 26% SCC. 37 (40%) had stage I, 29 (31%) stage II, and 20 (22%) stage III disease; 14 patients received neoadjuvant chemotherapy. Median tumor size was 4.0cm and 79 (85%) underwent R0 and 9 (10%) R1 resection. TIL expansion was 68% successful. Phenotypic and functional analysis of TIL is ongoing. Preliminary analysis show suppression of intratumoral CD8[+] cells with low perforin levels and high CD8[+]PD1 levels as compared to normal tissue; however tumor CD8[+]CD28 co-stimulatory molecule expression was high. PDX success rate is 35%. IHC analyses show higher CD8[+]PD1, CD3, CD8[+]BTLA expression in SCC than in adenocarcinoma or normal tissue. WES and RNA sequencing show that median mutation burden is 9.3/MB in adenocarcinomas and 11.2/MB in SCC. Other immunogenomic analyses are in process.
    
    Conclusion:
    The ICON is an ambitious multi-team project designed to integrate multiple levels of tumor related data. Preliminary analysis demonstrates the project to be feasible, with a high rate of prospective sample acquisition. Tumor profiles from ICON will serve as a reference for upcoming neoadjuvant single and dual checkpoint immunotherapy trials. ICON Team: A. Weissferdt, A. Vaporciyan, A. Futreal, T. Karpinets, C. Yee, C. Haymaker, L. Federico, M.-A. Forget, G. Lizee, A. Talukder, J. Roszik, H. Tran, M. Vasquez, E. Prado, C. Behrens, E. Parra, J. Rodriguez-Canales, J. Fujimoto, L. Vence, J. Roth, I. Meraz, E. Roarty, L. Lacerda, L. Byers, S. Swisher, W. William Jr., P. Sharma, J. Allison, B. Fang, H. Wagner, E. Bogatenkova, I. Wistuba, J. Heymach and C. Bernatchez
    
    

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