Purpose: We conducted a Phase II clinical trial with randomized patients to determine whether autologous formalin-fixed tumor vaccine (AFTV) protects against postsurgical recurrence of hepatocellular carcinoma (HCC).Experimental Design: Forty-one patients with HCC who had undergone curative resection were randomly allocated to the vaccine treatment (n ‫؍‬ 19) or no adjuvant control group (n ‫؍‬ 22). Three intradermal vaccinations were administered at 2-week intervals beginning 4 -6 weeks after hepatic resection. A delayed-type hypersensitivity test was performed before and after vaccination. Primary and secondary end points are recurrence-free survival and overall survival, respectively. Observation continued until the majority of surviving patients had lived >12 months after the curative resection.Results: In a median follow-up of 15 months, the risk of recurrence in vaccinated patients was reduced by 81% (95% confidence interval, 33-95%; P ‫؍‬ 0.003). Vaccination significantly prolonged the time to first recurrence (P ‫؍‬ 0.003) and improved recurrence-free survival (P ‫؍‬ 0.003) and overall survival rates (P ‫؍‬ 0.01). AFTV played a significant role in preventing recurrence in patients with small tumors. Adverse effects were limited to grade 1 or 2 skin toxicities such as erythema, dry desquamation, and pruritus.Conclusions: AFTV therapy is a safe, feasible, and effective treatment for preventing postoperational recurrence of HCC. Patients with low tumor burdens benefit from the treatment. This treatment should be advanced to a largescale randomized trial.

We developed a tumor vaccine consisting of fixed hepatocellular carcinoma (HCC) cells/tissue fragments, biodegradable microparticles encapsulating granulocyte-macrophage-colony stimulating factor and interleukin-2, and an adjuvant. The vaccine protected 33% of syngeneic mice from HCC cell challenge. The vaccine containing human autologous HCC fragments showed essentially no adverse effect in a phase I/IIa clinical trial and 8/12 patients developed a delayed-type hypersensitivity (DTH) response against the fragments. Although 2 of 4 DTH-response-negative patients had recurrence after curative resection, the DTH-response-positive patients had no recurrence. The time before the first recurrence in the vaccinated patients was significantly longer than that in 24 historical control patients operated in the same department (P < < < <0.05). This formulation is a promising candidate to prevent recurrence of human HCC.

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Background: Most patients with hepatocellular carcinoma (HCC) have advancedstage disease at diagnosis. The prognosis for patients with HCC is very poor, especially for those with portal vein tumour thrombi (PVTT). The purpose of our study was to observe the prognostic value of PVTT and tumour-infiltrating regulatory T cells (Tregs) and the correlation between them. Methods:We examined 76 HCC specimens by immunohistochemistry for CD4+, CD8+ T cells and Foxp3+ Tregs. The survival of patients was prospectively followed up. Patients with HCC were grouped according to the formation of PVTT or Treg infiltration status. We performed a Kaplan-Meier survival analysis to observe the difference in prognosis between the groups. We analyzed the correlation of Treg expression with clinical and pathologic features.Results: Survival analysis revealed that both the disease-free survival rate and total survival rate after hepatic resection were significantly lower in patients in the PVTT group than those in the non-PVTT group (p = 0.026 and p = 0.022, respectively). Likewise, both the disease-free survival rate and the total survival rate were significantly lower in patients in the high Treg group than those in the low Treg group (p = 0.012 and p = 0.023, respectively). We found that intratumoural Tregs were associated with PVTT formation (p = 0.001) and that patients with high Treg infiltration had a higher percentage of PVTT formation. Conclusion:Patients with PVTT formation or high intratumoural Treg infiltration tended to have a poor prognosis. Intratumoural Treg was associated with formation of PVTT in patients with HCC. Contexte :Chez la plupart des patients atteints de carcinome hépatocellulaire (CHC), la maladie est au stade avancé au moment du diagnostic. Le pronostic de ces patients est très médiocre, en particulier en présence de thrombose tumorale de la veine porte (TTVP). Notre étude visait à observer la valeur pronostique des TTVP et des lymphocytes T régulateurs (Tregs) infiltrant la tumeur, ainsi que le lien entre eux.Méthodes : Nous avons examiné 76 spécimens de CHC par immunohistochimie pour déterminer la présence de lymphocytes CD4+, CD8+ T et Foxp3+ Tregs. Nous avons suivi de façon prospective la survie des patients. Les patients atteints de CHC ont été regroupés en fonction de la formation de TTVP ou de l'état d'infiltration par les lymphocytes Treg. Nous avons procédé à une analyse de Kaplan-Meier de la survie pour observer la différence au niveau du pronostic entre les groupes. Nous avons analysé le lien entre l'expression des lymphocytes Treg et les caractéristiques cliniques et pathologiques.Résultats : L'analyse de la survie a révélé que le taux de survie exempte de maladie et le taux de survie total après une résection hépatique étaient beaucoup moins élevés dans les groupes des patients qui avaient une TTVP que dans le groupe de ceux qui n'en avaient pas (p = 0,026 et p = 0,022 respectivement). De même, le taux de survie exempte de maladie et le taux de survie total étaient tous deux beaucoup moins éle...