Yuliya Kitsel, MD
Postdoctoral Research Fellow
Memorial Sloan Kettering Cancer Center
Disclosure(s): No financial relationships to disclose
Constantinos T. Sofocleous, MD PhD
Weill Cornell Medical College Memorial Sloan-Kettering Cancer Center
The purpose of this study is to investigate the levels of circulating peripheral blood cytokines after yttrium-90 (Y90) transarterial radioembolization (TARE) of colorectal cancer liver metastases (CLM) using a range of radiation doses.
Materials and Methods:
Peripheral blood samples were collected from 7 patients immediately prior to (Pre), immediately after (T0), 3 weeks after (T3), and 6 weeks (T6) after TARE. The plasma samples were assessed using the Meso Scale Discovery multiplex cytokine immunoassay platform to calculate the levels of IFN-g (secreted in response to antigen, increases MHC expression and antigen presentation by all cells), TNF-a (activates endothelium, causes WBC recruitment, vascular leak), IL-1b (causes fever, acute inflammation, activates endothelium to express adhesion molecules, induces chemokine secretion to recruit WBCs), IL-2 (stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells), IL-4 (induces differentiation of T cells into Th2 cells, promotes growth of B cells, enhances class switching to IgE and IgG), IL-6 (causes fever and stimulates production of acute-phase proteins), IL-8 (major chemotactic factor for neutrophils), IL-10 (inhibits dendritic cells and activated macrophages, decreases expression of MHC class 2), IL-12p (induces differentiation of T cells into Th1 cells, activates NK cells), and IL-13 (promotes IgE production by B cells, induces alternative macrophage activation).
Decreased IFN-g was recorded in peripheral blood samples at T0 in all patients and increased by 280 times at T3 and T6 post TARE. IL-10 was decreased at T3 by an average of 54%. In 6 of the 7 patients, we noticed increased IL-8 after TARE. 3 of these 7 patients received high average local deposition doses (917.2 Gy, 1772 Gy, and 1768 Gy) for radiation segmentectomy without increased acute inflammatory cytokines (IL-1b, IL-6, TNF-a).
IFN-g, IL-8 and IL-10 showed the most pronounced changes after Y90 TARE of CLM. In this small group no linear relationship between Y90 dose and humoral immune response was observed.