Immune Checkpoint Blockade in Hepatocellular Carcinoma: 2017 Update

Abstract

releasing molecules such as perforin and granzymes (the effector phase) (fig 1) [10]. Moreover, recognition of TAAs by T cell receptors (TCR) triggers the release of interferon gamma (IFN-γ) and other cytokines by CD8-positive T cells in an attempt to attack the cancer. However, tumor cells protect themselves by expressing IFN-γ induced PD-L1 or PD-L2, which binds to PD-1. When this happens, PD-1/PD-L1 binding attenuate the antitumor immune response, thereby weakening the attacking power of the T cells. This is called immune escape or immune tolerance ( fig. 2). The anti-PD-1 antibody blocks PD-1 on activated T cells from binding to PD-L1 or PD-L2 on APCs or tumor cells. This removes the "brake" on the immune system and restores the ability of T cells to attack tumor cells ( fig. 3). Unlike conventional chemotherapy or molecular targeted therapy, anti-PD-1 antibody achieves its antitumor effect by restoring the original potential of the natural human immune system as a powerful and precise weapon against cancer cells [11][12][13][14][15][16][17][18][19][20][21][22]. Antibodies against PD-L1 expression in the cancer tissue are believed to have a similar effect [23]. The recognition of "immuno-oncology" using immune checkpoint inhibitors was considered the "Breakthrough of the Year" by the American journal Science in 2013, and immuno-oncology has been widely publicized. PD-L1 also serves as a biomarker that predicts the response to anti-PD-1 antibody [24]. In addition, Kupffer-phase Sonazoid contrast-enhanced ultrasonography is an effective imaging method for predicting the response to treatment with anti-PD-1 antibody [25]. Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma (HCC)Promising results from an interim analysis of a phase I/II trial of the anti-PD-1 antibody nivolumab (CheckMate-040 trial dose-escalation cohort) were presented at the

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

“…Among the patients who exhibited HFS, those who were able to receive post-progression treatment after sorafenib therapy had good OS, which suggests that addressing this side effect is important for preserving the remaining hepatic reserve. The recent success of new systemic therapy agents [33,34] and immunotherapies [35] will be expected to further improve survival among patients with advanced HCC.…”

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2)

“…However, in previous combination studies with TACE, the median OS ranged from 18 months (shortest) to 32 months (longest) ( Table 1 ), suggesting that the duration of the study needs to be extremely long when evaluating OS as a primary endpoint. In clinical studies that are terminated early because of tumor progression or adverse effects, patients often receive various post-trial treatments, such as hepatic artery infusion chemotherapy [20][21][22] , ablation [23][24][25] , or systemic therapy [26][27][28][29] . In such cases, post-trial treatment likely affects OS, making it difficult to evaluate treatment outcomes using OS, especially in studies of TACE in patients with intermediate-stage HCC.…”

Immune Gene Expression Profile in Hepatocellular Carcinoma and Surrounding Tissue Predicts Time to Tumor Recurrence

“…The success of immune checkpoint inhibition in solid tumors has prompted its application in HCC [7], but reliable biomarkers for prognosis and the identification of patients responsive to immunotherapies are still needed. In the attempt of treatment optimization, the expression of therapeutic targets such as PD-L1 has been tested, showing a low positive and negative predictive value [8].…”