Scientists have discovered that the effectiveness of chemotherapy can be significantly improved by combining it with immunotherapy to eliminate senescent cells. Senescent cells, also known as “zombie cells,” are generated as a result of cancer treatments, such as chemotherapy, and create a supportive environment for the growth of tumor cells that survive the treatment.
A team of researchers led by Dr. Manuel Serrano at IRB Barcelona conducted a study published in Nature Cancer, which revealed that senescent tumor cells activate the PD-L2 protein, protecting themselves from the immune system and recruiting immune suppressor cells. This leads to the formation of an inhibitory environment that impairs the ability of lymphocytes to kill cancer cells.
To investigate the impact of blocking PD-L2, the researchers removed PD-L2 from senescent cells and observed that these cells were rapidly eliminated by the immune system. By preventing senescent cells from creating an immunosuppressive environment, the lymphocytes retained their full capacity to kill any cancer cells that may have survived chemotherapy.
Dr. Manuel Serrano, who is currently based at Altos Labs in Cambridge, United Kingdom, stated that blocking PD-L2 made chemotherapy more effective against cancer. This discovery opens the possibility of using PD-L2 inhibitors as adjuvants in cancer treatment.
The study was conducted using cell lines and animal models of melanoma, pancreatic cancer, and breast cancer. Cellular senescence is a natural process that occurs during aging and is commonly observed in cancer therapies. The majority of cancer treatments, including chemotherapy and radiotherapy, cause extensive cellular damage and contribute to the formation of senescent cells within tumors. The research team intends to investigate whether senescent cells associated with organism aging also exhibit elevated levels of PD-L2.
While further experiments are needed to fully understand the role of PD-L2 in different types of human cancers, this study has provided valuable insights into the role and interaction of PD-L2 and senescent cells with the immune system. Dr. José Alberto López, a postdoctoral researcher at the same laboratory and co-author of the study along with Dr. Selim Chaib, explained that this research enhances our understanding of PD-L2 and its impact on the immune system.
Dr. López will establish a new laboratory at the Salamanca Cancer Research Center in 2024, which is a collaboration between the University of Salamanca and CSIC. Dr. Chaib is currently affiliated with the Mayo Clinic in Minnesota, United States.
The study was conducted in collaboration with groups led by Drs. Joaquín Arribas, Alena Gros, and María Abad at the Vall d’Hebron Institute of Oncology (VHIO). Dr. Arribas now serves as the director of the Hospital del Mar Research Institute (IMIM), while Dr. Abad is affiliated with Altos Labs.
Significant contributions to this study were also made by the team led by Drs. James Kirkland and Tamara Tchkonia at the Mayo Clinic. The research involved the participation of Rejuveron Senescence Therapeutics, a company developing antibodies against PD-L2 for clinical use, with central offices in Zurich and Barcelona.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
