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A study by MD Anderson researchers is shedding new light on how the protein PD-L1 suppresses the immune system, which may help scientists find new ways to identify and treat cancers associated with inflammation earlier.

Led by  chair of Molecular and Cellular Oncology, the study focused on breast cancer using mice and human tissue samples. The findings may also benefit various inflammation-caused cancers, including lung, colorectal, esophageal, pancreatic, melanoma and liver.

The researcher team¡¯s results demonstrated a previously unknown immunosuppression mechanism in cancer cells by which inhibition of the protein CSN5 activity stopped the ability of PD-L1 to evade the immune system. CSN5 impacted PD-L1¡¯s interaction with PD-1, a cell receptor that prevents T-cell activation when it binds to PD-L1. Many of today¡¯s powerful checkpoint blockade therapies that remove the ability of certain molecules to block the immune are based on this protein pairing.

¡°Because PD-1 and PD-L1 blockade have yielded such promising clinical effects, understanding the regulatory mechanism of PD-L1 may identify biomarkers and possibly lead to development of new combination therapies,¡± Hung said.

Also involved in this complex cellular interplay was the cell-signaling protein TNFa, which was shown to play a role in CSN5¡¯s ability to ¡°stabilize¡± PDL1 and enhance its interaction with PD-1 to allow cancer cells to escape from T-cell killing activity.

¡°This regulatory event is critical for breast cancer cells to escape immune surveillance via interaction between PD-L1 and PD-1,¡± Hung said. ¡°Importantly, inhibition of TNFa-mediated PD-L1 stabilization in cancer cells promotes the tumor-infiltrating immune response. Thus, targeting cancer cell PD-L1 stabilization through CSN5 inhibition could help us develop better treatments for cancer accompanied by inflammation.¡±