PD1+ Treg cell remodeling promotes immune homeostasis within peripheral blood and tumor microenvironment after microparticles-transarterial chemoembolization in hepatocellular carcinoma.

Abstract

The effects of transarterial chemoembolization (TACE) on the systemic immune in hepatocellular carcinoma (HCC) are not well understood. We aimed to reveal the temporal and spatial changes in the immune profile of peripheral blood and tumor tissues in HCC patients following TACE. Eighty-four HCC patients were included, 20 of whom received TACE with a median follow-up of 28 months. Immune cell proportion within peripheral blood was profiled with flow cytometry, and therapeutic efficacy was evaluated by imaging examinations. Additionally, cell distribution within tumor microenvironment (TME) were compared between the necrotic tumor infiltration zone (N-IZ) and the residual tumor infiltration zone (R-IZ) by multiplex immunofluorescence. Among 20 patients, 25% (5/20) achieved complete response, and 75% (15/20) showed partial response. Fourteen patients received combinational targeted therapy and immunotherapy and the median progression-free survival was 15.5 months. Compared to healthy individuals, HCC exhibited significantly higher proportions of regulatory T cells (Tregs) and programmed death-1 receptor (PD1)⁺ Tregs within peripheral blood. PD1⁺ Treg cells, PD1⁺ CD4⁺ T cells and PD1⁺ CD8⁺ T cells decreased significantly within peripheral blood after TACE. In TME, N-IZ showed significantly lower CD4⁺ T, CD8⁺ T and FOXP3⁺ Tregs, higher PD1⁺ CD8⁺/CD8⁺ and PD1⁺ CD8⁺/ PD1⁺ FOXP3⁺. Moreover, the spatial distance between CD8⁺ T cells and the nearest FOXP3⁺ Tregs in N-IZ was significantly greater than in R-IZ. Our findings demonstrated that TACE could both remodel the immune components in peripheral blood and TME, strengthening the rationale for developing immunotherapy alongside TACE.