Innovations and breakthroughs This study significantly find protocol promotes our understanding of the novel proteases DPP8 and DPP9 in lymphocytes, hepatocytes and liver injury. The authors showed that DPP8 and DPP9 were widely expressed in lymphocyte subpopulations and were upregulated in activated lymphocytes in a time dependent manner. The authors also demonstrated potential involvement of DPP8 and DPP9 in lymphocyte apoptosis. In liver, the authors showed that DPP8 and DPP9 expression levels were altered in liver injury and confirmed their role in the regulation of epidermal growth factor in hepatocytes, a mitogen that is considered crucial for hepatocyte proliferation and liver regeneration. Applications This study suggests that DPP8 and DPP9 have fundamental roles in the immune system, in lymphocyte activation and in apoptosis and they could be involved in chronic liver injury pathogenesis.

Terminology DPP4 enzyme activity is a specialized proteolytic enzyme activity that cuts two amino acids from the N-terminus of each target peptide, usually cutting after a proline residue; Lymphocyte activation is a cellular process that leads to a radical shift
Hepatocellular carcinoma (HCC)2 is the fifth most common cancer and the third leading cause of cancer death worldwide (1). Advanced or recurrent HCC is frequently resistant to conventional chemotherapeutic agents and radiation, and thus remains one of the most difficult cancers to treat (2).

Sorafenib, a multi-targeted receptor tyrosine kinase (RTK) inhibitor that targets the Raf kinases and other kinases such as VEGFR1�C3, PDGFR-��, FLT-3, and c-kit (1, 3�C4) has shown survival benefits in patients with advanced HCC and was approved for use in HCC by the United States Food and Drug Administration in 2007 (5�C7). However, sorafenib only provides a modest effect, prolonging survival in patients with HCC from a median 7.9 to 10.7 months. Therefore, more effective new drugs are still urgently needed for HCC. Autophagy, also known as type II programmed cell death (PCD), refers to an evolutionarily conserved catabolic process in which a cell degrades long-lived proteins and damaged organelles including the endoplasmic reticulum, Golgi apparatus, and mitochondria. In contrast with apoptosis, autophagy Batimastat is dependent on the presence of autophagosomes and autolysosomes, as well as an intact nucleus in the cell (8). Many reports have demonstrated that autophagy is not only a survival response to either growth factor or nutrient deprivation but also an important molecular mechanism for tumor cell suicide (9). Recent studies have revealed that autophagy has an active role in cell death and is a response to various anticancer therapies in many kinds of cancer cells (6).