Immune Checkpoint Inhibitors for the Treatment of Hepatocellular Carcinoma
Immune checkpoints are membrane-bound molecules that provide fine-tuning of the complex process of immune response against cancer. From a therapeutic perspective, interaction with checkpoint molecules has revolutionized the field of cancer therapy. Attention has focused in two players, CTLA-4 and PD-1. The former is essential for the activation of CD4+ T cells and the priming phase of the immune response while the latter inhibits CD4+ and CD8+ T cell activation. In patients with hepatocellular carcinoma, there is substantial evidence that supports a relevant role of immune checkpoints in the absence of an effective antitumor immune response. These negative signals can be blocked with the use of monoclonal antibodies. While CTLA-4 blockade first produced encouraging signals of antitumor activity, PD-1 blockade results in consistent tumor responses and prolonged stabilizations that lead to substantial prolongation of survival among patients with advanced tumors. This has fueled the interest in developing better therapeutic strategies through combinations of immune-oncology agents and combinations of such agents with targeted agents that may act synergistically.
Conflicts of Interest
Bruno Sangro has received consulting and/or lecture fees from Adaptimmune, Astra Zeneca, Bayer Healthcare, Bristol-Myers-Squibb, and Medimmune.
Delia D’Avola is the recipient of the Grant for Study Expansion from the Spanish Association for the Study of the Liver (Asociación Espanola para el Estudio del Hígado AEEH) and Cancer Research Grant from Nuovo Soldati Foundation. This work was supported by EC FP7 Project Cancer Vaccine development for Hepatocellular Carcinoma – HEPAVAC (Grant Nr. 602,893), EC H2020 Project Immunology and Immunotherapy of cancer: strengthening the translational aspect – HepaMUT (Grant Nr. AC16/00165), and project PI16/01845, integrated in Plan Estatal de I + D + I 2013–2016 and co-financed by ISCIII-Subdirección General de Evaluación y Fomento de la investigación and Fondo Europeo de Desarrollo Regional (FEDER).
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