**Zuzana Macek Jilkova 1,2,3,\* , Caroline Aspord 1,2,4 and Thomas Decaens 1,2,3,\***


Received: 27 August 2019; Accepted: 10 October 2019; Published: 14 October 2019

**Abstract:** Immunotherapies targeting immune checkpoints are fast-developing therapeutic approaches adopted for several tumor types that trigger unprecedented rates of durable clinical responses. Immune checkpoint programmed cell death protein 1 (PD-1), expressed primarily by T cells, and programmed cell death ligand 1 (PD-L1), expressed mainly by tumor cells, macrophages, and dendritic cells, are molecules that impede immune function, thereby allowing tumor cells to proliferate, grow and spread. PD-1/PD-L1 checkpoint inhibitors have emerged as a promising treatment strategy of hepatocellular carcinoma (HCC). However, only a minority of HCC patients benefit from this therapy. To find a niche for immune checkpoint inhibition in HCC patients, future strategies might require predictive factor-based patient selection, to identify patients who are likely to respond to the said therapy and combination strategies in order to enhance anti-tumor efficacy and clinical success. This review provides an overview of the most recent data pertaining to predictive factors for response to PD-1/PD-L1 checkpoint inhibition in the field of HCC.

**Keywords:** PD-1; PD-L1; hepatocellular carcinoma; predictive factors; immunotherapy; immune checkpoint inhibition
