Abstract 5596: Dynamic monitoring of plasma DAMP proteins during multimodal anticancer treatment in advanced lung cancer patients

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Abstract Immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs) from dying cancer cells is a potential contributor to the synergistic antitumor effects of the combination of cytotoxic chemotherapy with immune checkpoint blockade. However, little information on the kinetics of circulating DAMP levels in cancer patients has been available. We evaluated the possible effects of various anticancer treatment modalities on the kinetics of plasma DAMP proteins in lung cancer patients. In a prospective observational study, plasma concentrations of three representative DAMP proteins–high-mobility group box 1 (HMGB1), calreticulin (CRT), and histone H3–in 50 patients with advanced lung cancer were measured at five time points during the first cycle of anticancer therapy by ELISA assay. The plasma levels of HMGB1 and CRT increased during the first treatment cycle in 42 (84%) and 35 (70%) patients, respectively, with these increases being detectable as early as day 3. The maximum fold changes in HMGB1 and CRT concentrations was associated with clinical response. Among the various treatment modalities, cytotoxic chemotherapy induced the greatest increases in the concentrations of these DAMPs. There was no correlation between the maximum fold changes in the plasma levels of HMGB1 and CRT. Meanwhile, histone H3 was essentially undetectable in most patients. In conclusion, serial monitoring of plasma revealed that anticancer treatment modalities increased the circulating levels of DAMPs with their association with clinical response, suggesting that agents capable of increasing the release of DAMPs into plasma might induce immunogenic cell death in advanced lung cancer patients. Citation Format: Hiroyuki Inoue, Hirono Tsutsumi, Yoshimasa Shiraishi, Koji Okamura, Yoichi Nakanishi, Isamu Okamoto. Dynamic monitoring of plasma DAMP proteins during multimodal anticancer treatment in advanced lung cancer patients [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 5596.