Systemic Immunological Changes After Yttrium-90 Radioembolization: A Pilot Prospective Observational Study-Clinical...

To prospectively investigate levels of circulating cytokines, changes in frequencies of various immune cell subsets and expression of proliferation and checkpoint molecules on T cells in the peripheral blood after yttrium-90 radioembolization (TARE) of colorectal cancer liver metastases (CLM).

We prospectively collected, isolated, and froze peripheral blood mononuclear cells (PBMC) and plasma samples from 15 patients immediately before, immediately after, 3 and 6 weeks post-TARE of CLM. Plasma samples were assessed for various cytokines using a multiplex immunoassay platform. PBMC samples were analyzed in a monocyte/dendritic cell (DC)/B cell flow panel and a T cell activation/exhaustion flow phenotyping panel. We compared the levels at the respective time points using Wilcoxon signed rank test.

IFN-g significantly decreased immediately after (mean 1.62 vs. 3.02 at baseline, p = 0.04) and increased at 6 weeks compared to the immediately post-TARE nadir (mean 9.42 vs. 1.62, p = 0.04). IL-10 decreased at 3 weeks (mean 0.36 vs. 1.75, p = 0.025) post-TARE compared to baseline. Increased CD3⁺T cells (mean 78.24 vs. 60.8, p = 0.002) and decreased CTLA-4⁺CD4⁺T cells (mean 2.58 vs. 4.41, p = 0.033) were observed at 3 weeks compared to baseline. Increased Ki-67⁺ proliferating CD8⁺T cells at 3 and 6 weeks (mean 7.28 and 9.06, respectively, vs. 3.93 at baseline, p = 0.02 and 0.03) were recorded.

A shift toward a favorable antitumoral cytokinic and immune cells response was observed after TARE. Significant changes were in specialized immune cells subsets playing important roles in the activation of the immune system. These results support trials combining TARE with immunotherapy for patients with CLM.