Abstract PO-070: What kills patients with severe Covid-19 might also kill patients with terminal cancer

Abstract

Abstract Introduction: As a prominent clinical feature of severe Covid-19, cytokine storm has attracted enormous attention recently. It is generally believed that cytokine storm might be the underlying force leading to health exacerbation and death from severe Covid-19. However, the role of cytokine storm in terminal cancer has not been reported. In this study, we investigated the role of cytokine storm in a murine tumor model that mimics the disease progression of terminal cancer. We found that cytokine storm develops in terminal cancer and leads to cachexia, which is a prevalent and lethal syndrome of terminal cancer. Methods: 7-week old BALB/c mice were inoculated with 1 x106 C26 tumor cells subcutaneously. Mice body weight and health condition were monitored starting 7 days after tumor inoculation. At various time points, serum cytokines were measured, immune cells were analyzed with flow cytometry, and multiple organs were collected and processed for histopathologic assessment. Results: Growth of subcutaneously inoculated tumors without metastasis progressively induces host body weight loss and overall health deterioration. Cytokine storm characterized by elevated expression of multiple proinflammatory cytokines such as IL-1, IL-6, and TNF-a in blood develops accompanying the health deterioration. In parallel with cytokine storm development, massive infiltration of Gr-1 positive cells occurs in vital organs (lung and liver) and brings severe tissue damage. Histopathologic check ruled out any tumor metastasis to these organs, which suggests that the inflammatory response is the cause of the multiple organ damage. Importantly, suppression of the inflammatory response with interventions can completely reverse the cachexia syndrome and increase survival. Conclusions and Implication: Cytokine storm develops and plays an important role in the health exacerbation of terminal cancer. Therefore, calming the cytokine storm with interventions that can suppress the inflammatory response might represent a new and promising approach to the treatment of terminal cancer. This approach may have the potential to save many patients from imminent deaths, which are often not directly caused by organ occupation. Citation Format: Lingbing Zhang. What kills patients with severe Covid-19 might also kill patients with terminal cancer [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-070.