Abstract 1326: Elevated levels of plasma VEGF associated with the attenuation of whole blood IFN-γ production and QOL impairment in patients with advanced gastric cancer
Authors: Naoyuki Sakamoto, Takeshi Ishikawa, Tetsuya Okayama, Tomoyo Yasuda, Toshifumi Doi, Hideyuki Konishi, Satoshi Kokura, Mari Tanigawa, Kazuko Uno, Yuji Naito, Yoshito Ito, Toshikazu Yoshikawa
Journal: Cancer Research (2015)

Abstract Introduction: Gastric cancer is one of the leading types of cancer and the second leading cause of cancer death in the world. Recently, the foci of treatment shift towards not only survival benefit but also better quality of life (QOL) in patients with advanced gastric cancer. Therefore, the development of an auxiliary tool to assess QOL is likely to be required. On the other hand, immune checkpoint blockade by anti-CTLA-4 antibody and anti-PD-1 antibody led to clinical breakthrough for the treatment of patients with advanced cancer. Early phase clinical trial of pembrolizumab in patients with advanced gastric cancer has already been conducted. Pretreatment circulating VEGF have been recently shown to associate with clinical outcome in patients treated with ipilimumab. Certain circulating cytokine levels have been shown to reflect tumor progression and have a prognostic value. Although, it remains obscure whether circulating cytokine levels affect QOL and immune function. In this study, we examined the correlation of circulating cytokine with QOL as well as parameters of immune function such as whole blood cytokine production and the number of peripheral Tregs in patients with advanced gastric cancer. Methods: Subjects comprised 31 patients with unresectable or recurrent gastric cancer. We evaluated plasma cytokine levels and whole blood cytokine production after phytohemagglutinin (PHA) stimulation using the bioplex array system. We also assessed the number of peripheral Tregs by flow cytometry. Health-related QOL was assessed using the Quality of Life Questionnaire (EORTC QLQ-C30). Results: Significant negative correlation was found between plasma VEGF levels and global health status scores (p = 0.0103) as well as physical functioning scale scores (p = 0.0006) and cognitive functioning scale scores (p = 0.0191). Some symptom scale scores (e.g. fatigue, appetite loss) were correlated with plasma VEGF levels. There was a negative correlation between plasma VEGF levels and whole blood IFN-γ production (p = 0.0002). Significant negative relationship existed between the number of peripheral Tregs and plasma IL-6 levels (p&amp;lt;0.0001). We confirmed that PBMCs-secreted IFN-γ after PHA stimulation reduced by the exposure to recombinant VEGF in vivo. Conclusion: These data indicate that the evaluation of plasma VEGF level is likely to be useful to assess QOL such as global health status, physical functioning and cognitive functioning and elevated levels of plasma VEGF might associated with the attenuation of immune function in patients with advanced gastric cancer. Consequently, clinical utility of anti-VEGF therapy combined with immunotherapy is required to investigate in larger clinical studies in the future. Citation Format: Naoyuki Sakamoto, Takeshi Ishikawa, Tetsuya Okayama, Tomoyo Yasuda, Toshifumi Doi, Hideyuki Konishi, Satoshi Kokura, Mari Tanigawa, Kazuko Uno, Yuji Naito, Yoshito Ito, Toshikazu Yoshikawa. Elevated levels of plasma VEGF associated with the attenuation of whole blood IFN-γ production and QOL impairment in patients with advanced gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2015-1326