DPP9 (Dipeptidyl Peptidase 9)

Consistently, we observed increasing DPP8/9 activity during B-cell maturation. Overall, DiPAK is a versatile tool for real-time single-cell monitoring of DPP8/9 activity in a broad range of cells and organisms.

The tumour suppressor protein p53 was increased and the autophagy proteins beclin1, LC3B and p62 were altered. In conclusion, hepatocyte-specific DPP9 gene deletion in experimental primary liver cancer improved energy metabolism and may reduce liver cancer initiation, via mechanisms that may include increased autophagy and tumour suppression.

In absence of DPP9, the EMT transcription factor ZEB1 was stabilized due to insufficient degradation by the proteasome. In summary, low expression of DPP9 appears to decelerate mammary tumorigenesis but favors EMT and metastasis, which establishes DPP9 as a novel dynamic regulator of breast cancer initiation and progression.

This review summarizes most of the current evidence that DPP4/9 is associated with lung disease. Within the DPP4 family, the role of DPP4 in particular in respiratory disease is important.

Moreover, DPP9 overexpression suppressed ferroptosis and induced resistance to sorafenib in ccRCC cells, which was largely dependent on the NRF2 transcriptional target SLC7A11. Collectively, these findings indicate that the accumulation of DPP9 results in hyperactivation of the NRF2 pathway to promote tumorigenesis and intrinsic drug resistance in ccRCC.

Conclusions DPP9 can up-regulate the expression of PD-L1 in renal cancer cells through dynamically adjusting the stability of the BRISC complex via SHMT2. We provide the clinical principle and mechanism of DPP9 inhibitor combined with PD-L1 monoclonal antibody, and further determine the patient population suitable for immunotherapy.

Additional biomarker analyses are ongoing to build on this finding. It will also be validated in the randomized Phase 2b SCNC trial planned to initiate in 2H 2023.