Cancer treatments, while effective in eliminating tumor cells, can also inadvertently generate senescent tumor cells, known as zombie cells. These senescent cells create a favorable environment for the resurgence of tumor cells that may have survived chemotherapy. A team at IRB Barcelona has now uncovered a crucial mechanism involving the PD-L2 protein that shields senescent cells from the immune system and recruits immune suppressor cells.
Based on these findings, a team of IRB Barcelona scientists wondered what would be the effect of inactivating PD-L2.
The study, conducted on cell lines and animal models of melanoma, pancreatic and breast cancer and published in Nature Cancer, revealed that inactivating PD-L2 eliminates senescent cells rapidly. This interception prevents the creation of an immunosuppressive environment, allowing lymphocytes to retain their full capacity to eliminate escaped cancer cells. Dr. Serrano emphasizes the potential significance, stating,
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“By blocking PD-L2 in mouse models, we have seen that chemotherapy is more effective against cancer. This finding paves the way to consider the use of a potential PD-L2 inhibitor as an adjuvant in the treatment of this disease,” explained senior author Manuel Serrano,
“Although more experiments are needed to characterize the role of this molecule in different types of human cancers, this work has enhanced our understanding of the role of PD-L2 and the interaction of senescent cells with the immune system,” explained co-first author José Alberto López.