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Björn Kruspig



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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-14 - Developing an Immunogenic Model of Non Small Cell Lung Cancer (Now Available) (ID 1088)

      10:15 - 18:15  |  Author(s): Björn Kruspig

      • Abstract
      • Slides

      Background

      Lung cancer is the most common form of cancer in the world both in terms of new cases diagnosed and number of deaths, which totals ~1.5 million per annum. Patient prognosis has not improved significantly over the last 40 years, and the 10-year survival rate remains ~5%. Approximately 85% of lung cancers can be classified as non-small cell lung cancer (NSCLC), of which Lung Adenocarcinoma (LuAd) is the most common histological subtype. Specific DNA mutations allow for further molecular characterisation of LuAd, for example, activating mutations in KRAS have been described in one third of cases. The oncogene MYC is a downstream target of KRAS signalling and the two oncogenes have long been known to cooperate to induce tumorigenesis. The gene editing enzyme APOBEC3B has recently been recognised as an important mechanism for fuelling genetic diversity in cancer and has been shown to be upregulated in LuAd.

      Method

      The KRas-Myc (KM) mouse model of LuAd combines expression of mutant KrasG12D and modestly overexpressed c-MYC to drive the formation of autochthonous adenocarcinomas. Selective expression of KrasG12D and MYC are induced in the lung epithelium by intranasal inhalation. We have generated the KMA3B model of lung cancer in which APOBEC3B is selectively expressed in the KM model to generate tumours which have a modest overexpression of APOBEC3B. Using immunohistochemistry and FACs analysis we aim to identify the differences occurring in the KM and KMA3B models and investigate the implications of these differences.

      Result

      Preliminary results show an increase in CD8+ T cell infiltration has been noted in the KMA3B lungs when compared with their KM counterparts at an 8 week time point. We hypothesize that the presence of APOBEC3B results in an increased number of mutated peptides leading to increased neo-antigen presentation, and a more effective immune response to the tumours. Indeed, survival data indicates that introducing APOBEC3B to the KM genetic background extends survival by 50%. FACs analysis using a panel designed to identify T cells and their activation status indicates differences in the populations of T cells present in KMA3B vs KM tumours.

      Conclusion

      We show that the modest overexpression of APOBEC3B in a KM background increases the lifespan of the mice. This increase in survival appears to correlate with an increase in cytotoxic T cell surveillance. The implications and utility of this model will be discussed.

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