2024-01-30 09:45:34
Cancer treatment, whether by chemotherapy or other targeted therapies, in addition to causing the death of a large number of tumor cells, results in the formation of senescent tumor cells. These cells (also called “zombies”) do not reproduce, but unfortunately they generate a favorable environment for tumor regrowth.
Researchers from the Biomedicine Research Institute (IRB Barcelona), led by Dr. Manuel Serrano, have described how cancer cells that have become senescent after treatment activate the PD-L2 protein to protect themselves from the immune system, while at the same time They recruit suppressor cells of the immune system. These suppressor cells create an inhibitory environment that prevents lymphocytes from accessing and acting against cancer cells. Senescent cells thus 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 Dr. Manuel Serrano, currently a researcher at Altos Labs (Cambridge, United Kingdom).
The study has been carried out with cell lines and animal research models of skin, pancreatic and breast cancer.
Senescence, a common phenomenon in cancer therapies
Cellular senescence is a process that occurs naturally in aging and has emerged as a common phenomenon in the context of cancer therapies. Most oncological therapies (such as chemotherapy or radiotherapy) act by causing multiple cellular damage and, as a consequence, cause senescent cells, particularly within the tumor. The scientific team will now study whether senescence linked to the aging of the organism is also correlated with elevated levels of PD-L2.
“Although more experiments are needed to characterize the role of this molecule in different human tumors, this work has allowed us to expand our knowledge about the role of PD-L2 and the interaction of senescent cells with the immune system,” explains Dr. José. Alberto López, postdoctoral researcher from the same laboratory and first author of the work together with Dr. Selim Chaib. In 2024, Dr. López will open a new laboratory at the Salamanca Cancer Research Center, a joint center of the University of Salamanca and the CSIC. Dr. Chaib is now a researcher at the Mayo Clinic, in Minnesota (United States).
Senescent human melanoma tumor cells. In brown, the PD-L2 protein, which acts as a protective shield and prevents the action of the immune system. (Image: IRB Barcelona. CC BY-NC-ND)
This work has been carried out in collaboration with the groups of doctors Joaquín Arribas, Alena Gros and María Abad at the Vall d’Hebron Institute of Oncology (VHIO). Dr. Arribas also directs the Hospital del Mar Research Institute (IMIM) and Dr. Abad works at Altos Labs. The team led by doctors James Kirkland and Tamara Tchkonia from the Mayo Clinic have contributed important data to this study. The company Rejuveron Senescence Therapeutics, with offices in Zurich and Barcelona, which is clinically developing antibodies against PD-L2, has also participated in the work.
The study is titled “The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2.” And it has been published in the academic journal Nature Cancer. (Source: IRB Barcelona)
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