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yixuan Wen

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      39P - High dose apatinib in the reversal of immunosuppressive tumor microenvironment for irradiation therapy in lung carcinoma (ID 161)

      12:30 - 13:00  |  Author(s): yixuan Wen

      • Abstract


      This study aimed to investigate the potential systemic anti-tumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Lewis lung cancer cells were injected into C57BL/6 mice in the right hindlimb (primary tumor; irradiated) and in the left flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Only primary tumor growth could be delayed with single SABR, while both primary and secondary tumor growth could be regressed with apatinib administration in a dose-dependent propensity. When combining SABR and apatinib, significant retardation of primary tumor growth could be observed. In addition, when combining SABR and apatinib of 200 mg/kg, growth of the secondary tumors could also be significantly inhibited (P < 0.01). This result indicated the namely “abscopal effect”. Mechanism analysis suggested that increased programmed death ligand-1 expression in tumor tissue was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed and tumor specific T cell activation could be induced. More importantly, this two-pronged approach evoked tumor antigen-specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Our results suggested that the tumor microenvironment could be managed with high-dose of apatinib, which was effective in eliciting an abscopal effect induced by SABR.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      This work was supported by National Natural Science Foundation of China grants 81472792 and 81702813, Postgraduate Research & Practice Innovation Program of Jiangsu Province grants SJCX18_0707, and the Technology Office Foundation of Lianyungang City (NO.SH1613).

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.