Abstract 2414: Immunogenic properties of chemotherapeutic agents in the treatment of non-small cell lung cancer
Authors: Tal Flieswasser, Jinthe Van Loenhout, Laurie Freire Boullosa, Astrid Van den Eynde, Jorrit De Waele, Jonas Van Audenaerde, Filip Lardon, Evelien Smits, Patrick Pauwels, Jacobs Julie
Journal: Cancer Research (2020)

Abstract Introduction. Accumulating evidence suggests that the clinical success of chemotherapy is not only attributed to direct tumor cell toxicity, but also relies on its anti-tumor effects by immunomodulation. In this regard, the concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, we assessed different chemotherapeutic agents on their ability to induce ICD in vitro and in vivo in non-small cell lung cancer (NSCLC). Material and methods. NSCLC cell lines (NCI-H1975, A549, NCI-H1650 and LLC) were treated with the IC50 of different chemotherapeutic agents: docetaxel (DOC), carboplatin (CARBO), cisplatin (CDDP), oxaliplatin (OXA) and mafosfamide (MF). In addition, combinations of DOC (IC50) with CARBO (IC40) or CDDP (IC40) were included. Release of important damage-associated molecular patterns (DAMPs) was evaluated: ATP (bioluminescence), ecto-CRT (flow cytometry) and HMGB1 (ELISA) after 24h, 48h and 72h of treatment, respectively. In addition, phagocytosis and maturation status of dendritic cells (DCs) were assessed. Finally, a vaccination assay was performed to validate in vitro findings using 6-week old female C57BL/6J mice (5 mice/condition). Mice were vaccinated twice (1 × 106 treated cells/mouse) before receiving the challenge (5 × 104 live cells/mouse). Results. Three out of four NSCLC cell lines (NCI-H1975, A549 and LLC) showed significant higher levels of ATP, ecto-CRT and HMGB1 after treatment with DOC, DOC+CARBO and DOC+CDDP compared to vehicle. In addition, phagocytosis of treated tumor cells and maturation (CD86) of DCs were significantly increased in all three human NSCLC cell lines after treatment with the above-mentioned chemotherapeutic regimens. Furthermore, murine LLC cells treated with DOC, MF, DOC+CARBO and DOC+CDDP resulted in a significant release of all three DAMPs in vitro, as opposed to treatment with OXA. Along similar lines, 0%, (DOC+CDDP), 20% (MF and DOC+CARBO) and 80% (OXA) of the mice developed a tumor at the challenge site in vivo. This was not the case for treatment with DOC, which resulted in tumor growth at the challenge site in 60% of the mice. Conclusion. Overall, these findings demonstrate the immunostimulatory effects of clinically relevant chemotherapeutic regimens, especially DOC+CARBO and DOC+CDDP, making it worthwhile to investigate these agents in combination strategies with immunotherapy in NSCLC. Citation Format: Tal Flieswasser, Jinthe Van Loenhout, Laurie Freire Boullosa, Astrid Van den Eynde, Jorrit De Waele, Jonas Van Audenaerde, Filip Lardon, Evelien Smits, Patrick Pauwels, Jacobs Julie. Immunogenic properties of chemotherapeutic agents in the treatment of non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2414.