Chemotherapy, more effective when senescent cells are eliminated through immunotherapy

Treat a Cancer either chemotherapy or other targeted treatments not only lead to the death of a large number of tumor cells, but also to the formation of senescent tumor cells. These cells, also called zombies, do not reproduce, but unfortunately create a favorable environment for tumors to grow again.

Researchers from IRB Barcelona led by Manuel Serranohave described how cancer cells that are senescent after treatment activate the PD-L2 protein to protect themselves from the immune system while recruiting immunosuppressor cells.

By blocking PD-L2, we have seen in mouse models that chemotherapy is more effective against cancer

Manuel Serrano, lead author

These suppressor cells create an inhibitory environment that prevents lymphocytes from accessing and acting against cancer cells. Senescent cells therefore promote tumor growth and limit the effectiveness of chemotherapy.

“By blocking PD-L2, we have seen in mouse models that chemotherapy is more effective against cancer. This opens the way to considering the use of a potential PD-L2 inhibitor as an adjuvant in the treatment of this disease,” explains Serrano, currently a researcher at Altos Labs (Cambridge, United Kingdom).

The study, published in the journal Natural cancerwas carried out using cell lines and animal models of skin, pancreatic and breast cancer.

Researcher José Alberto López, first author of the study. / IRB Barcelona

A common phenomenon in cancer therapies

Cellular senescence is a process that occurs naturally during aging and has been found to be a common phenomenon in the context of cancer therapies. Most of them (e.g. chemotherapy or radiation therapy) work by causing multiple cell damage and, as a result, the development of senescent cells, especially inside the tumor.

This work has allowed us to expand our knowledge of the role of PD-L2 and the interaction of senescent cells with the immune system.

José Alberto López, first author

The team will now investigate whether the senescence associated with organismal aging also correlates with increased PD-L2 levels.

“Although further experiments are needed to characterize the role of this molecule in various human tumors, this work has allowed us to expand our knowledge of the role of PD-L2 and the interaction of senescent cells with the immune system,” he concludes. Jose Alberto LopezFirst author of the work.