Percutaneous radiofrequency ablation (RFA) is one of the main treatments of small hepatocellular carcinoma (HCC). However, it remains unclear whether this local treatment can induce systemic immune variations.
We conducted a prospective study in a tertiary center including consecutive cirrhotic patients with unifocal HCC<5cm treated by a first RFA between 2010 and 2014. Peripheral blood mononuclear cells were isolated before (D0), day after (D1) and month after RFA (M1). Frequencies and phenotypes of myeloid cells, T cells and NK cells were compared between timepoints. Overall recurrence and associated variables were estimated using Kaplan-Meier, log-rank and Cox proportional-hazards models.
80 patients were included (69% male, median age: 67 years). Main etiologies of HCC were alcohol (51%), hepatitis C virus (45%), non-alcoholic steato-hepatitis (36%) and hepatitis B virus (9%). Median overall survival was 55M; median progression-free survival was 29.5M. Among innate immune populations, we observed variations between D0, D1 and M1 in NKp30+ NK cells (p < 0.0001) and in plasmacytoid dendritic cells (pDC, p = 0.0009). Concerning adaptive immunity, we observed variations in CD8 Central Memory (p = 0.006) and CD28+ CD8 Central Memory (p = 0.002). An early dynamic (D0/D1) of activated NKp30+ NK cells was associated with a decreased overall recurrence (log-rank, p = 0.016, median delay 25.1 vs 40.6 months). In contrast, a late dynamic (D1/M1) of immature NK cells (CD56bright) and altered myeloid DC (PDL1+) was associated with an increased overall recurrence (log-rank, p = 0.011 and p = 0.0044, respectively). In multivariate analysis, variation of immature NK cells predict tumor recurrence independently of classical clinical prognostic features (HR = 2.41, CI95%(1.15-5.057), p = 0.019).
Percutaneous RFA of small HCC leads to systemic modifications of innate and adaptive immunity closely linked with overall tumor recurrence.
Service d’Hépatologie, Hopital Jean Verdier.
Grant FAR from SNFGE (Société Nationale Française de Gastro-Entérologie).
N. Ganne-Carrié: Personal fees: Bayer Schering Pharma. D. Olive: Founder of Imcheck Therapeutics. All other authors have declared no conflicts of interest.