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Xiaoshan Zhang

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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-08 - Co-Residence of Patient-Derived Immune Cells in Patient-Derived Xenografts from Lung Cancer Patients (ID 11161)

      16:45 - 18:00  |  Author(s): Xiaoshan Zhang

      • Abstract


      Patient-derived xenograft (PDX) models have been shown to recapitulate many characteristics of human tumors and have been increasingly used for anticancer drug development, molecular characterization of cancer biology, and development of precision therapies. However, because PDXs are grown in immunodeficient mouse strains, they are regarded as inappropriate for preclinical evaluation of anticancer immunotherapy. Here we evaluated whether patient-derived immune cells co-exist in PDXs derived from lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      First-generation PDX (F1) was established by subcutaneously implanting human tumor tissue into non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mice with a null mutation of the gene encoding for interleukin-2 receptor g (NSG). When the resulting tumors in these mice grew to about 1.5 cm in diameter, we passaged the tumors in NSG or nude mice for subsequent generations. A small piece of these PDX tissues (about 2-3 mm3) were minced into fragments and cultured in media containing human interleukin-2 (IL-2) (2000 -6000 units/ml) for up to 6 weeks. The proliferated lymphocytes for analyzed by fluorescence-activated cell sorting (FACS) with antibodies specific for human immune cell surface markers. The provenance of cultured cells was determined by DNA fingerprinting assay together with patients’ DNA samples from primary tumors and/or peripheral blood mononuclear cells (PBMC).

      4c3880bb027f159e801041b1021e88e8 Result

      The mean time of PDX growth in NSG mice before harvesting for culturing tumor-infiltrating lymphocytes (TILs) was 120 days (ranging from 63-292 days). TILs were successfully cultured from 8 of 25 PDXs samples (about 32%), with one from F2 PDXs and 7 from F1 PDXs. TILs from five of those PDXs were predominantly human CD3+CD8+ T cells (72% -99%), while the remaining three were predominantly human CD19+ B cells (77% - 95%). DNA fingerprint analysis showed that genotypes of TILs were identical to patients’ primary tumors and/or PBMC, demonstrating that the TILs were from the same patients as the PDXs. Further analysis showed that CD8+ T cells from PDXs were CD45RO+, with either CD62L+ or CD62L-.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patient-derived immune cells co-exist with PDXs in some lung cancer PDX models. Most of those immune cells were CD3+CD8+ and could be memory T cells. These results suggest that some PDXs might be used for evaluating functions of tumor resident immune cells and/or for evaluating anticancer immunotherapies.