Scientists reveal new mechanisms for the expression of cancer immunotherapy drugs

The digestive group of Renji Hospital, affiliated with Shanghai Jiaobi University School of Medicine, reduced the expression of tumor cell PD-L1 by designing PD-PALM polypeptides, and provided a new idea for the development of immunochemic checkpoint inhibitors, which is expected to become an immunotherapy drug for tumors. The findings were published online online in Nature-Biomedical Engineering.
the journal is understood to have issued a commentary by senior cell biologist Professor Stephane Lefrancois, explaining in detail the scientific findings and implications of the work, arguing that "the use of peptide inhibitors to block PD-L1 palmylization suggests new targeting methods based on post-translation modification." This cell-penetrating peptide developed by Xu Jie's team significantly inhibits PD-L1 and therefore has the potential to become a therapeutic molecule."
immune checkpoints are inhibitory signaling path paths distributed in the body's immune system.
, "tumors can use the inhibition of immune checkpoint paths to evade the identification of immune cells," said Xu Jie, a researcher at the University of Shanghai. Therefore, inhibiting immune checkpoints can stimulate the immune system's original anti-tumor ability. However, immuno-checkpoint blocking therapy still has problems such as overall inefficiency, drug resistance after long-term use, and the occurrence of serious side effects.
Xu Jie told China Science daily that an in-depth study of the PD-L1 regulatory mechanism would help improve the effectiveness of treatment.
researchers have found that PD-L1 proteins can be palmylated by DHHC3 enzymes and reduce their ubiminization modification and lysosome degradation. Due to the lack of selectivity of DHHC enzymes in the small molecule inhibitors of palmylization, Xu Jie's team made a design attempt to design competitive inhibitors for palmylization and reduced the expression of tumor cell PD-L1 by designing PD-PALM polypeptides.
: "In the future, PD-PALM can also be modified and modified to further improve its activity and stability, enhance its potential for drug development." (Source: Science Network Huang Xin)
relevant paper information: