Cancer cells have long been a challenge for the immune system to identify and attack, as they create an environment that blocks immune cells and protects the tumor. However, a new study by scientists at the Institute for Research in Biomedicine (IRB) in Barcelona could change this.
According to a new study, published in the journal Cancer Discovery, inducing senescence in cancer cells could improve the effectiveness of the immune response to a greater degree than dead cancer cells, which have been the focus of research in the field for years.
The study, led by ICREA researcher Dr. Manuel Serrano and Dr. Federico Pietrocola, who is now at the Karolinska Institutet in Sweden, found that vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumors prevented the animals from developing cancer, or at least significantly reduced the number of cases.
The researchers also observed the efficacy of the vaccination in animals that had already developed tumors, and while the results were more moderate due to the protective barrier of the tumor, improvements were still observed.
“Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy,” explains Dr. Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.
The researchers tested the technique in animal models of melanoma, a type of cancer characterized by high activation of the immune system, and also in pancreatic cancer models, which present strong barriers against immune cells.
Prophylactic vaccination therapy with senescent cancer cells was effective against both types of tumors. They also complemented the study with tumor samples from cancer patients and confirmed that human cancer cells also have a greater capacity to activate the immune system when they are previously rendered senescent.
The study concludes that the induction of senescence in tumor cells improves the recognition of these cells by the immune system and increases the intensity of the response they generate. Senescent cells present unique signals that stimulate recognition by and activation of the immune system, which differ from those presented by cells before senescence has been induced.
The study conducted by the IRB Barcelona team has been published simultaneously and in the same journal as another article led by the Memorial Sloan Kettering Cancer Center (MSKCC) in New York and completed in collaboration with IRB Barcelona. The latter, which is authored by Dr. Direna Alonso-Curbello, now head of the Inflammation, Tissue Plasticity & Cancer laboratory at IRB Barcelona, and Dr. Scott W. Lowe, reach complementary conclusions despite studying the subject using a different approach.
The work by MSKCC focused on describing how the induction of senescence in tumor cells alters the molecular programs that mediate communication between the tumor and the immune system. “Until now, most studies have focused on the ability of senescent cells to “send” inflammatory signals to their environment.
Our work shows that this communication is bidirectional, revealing that senescence increases the ability of cells to “receive” signals from their environment that activate key pathways for their recognition and destruction by cytotoxic T cells,” explains Dr. Alonso-Curbello.
This work demonstrates that the ability to “receive” signals from the environment, which is increased by the induction of senescence, amplifies the anti-tumor effects of signals such as interferon, making tumor cells more visible to the immune system and reactivating anti-tumour immunity in liver cancer models.
The IRB Barcelona team is now studying the combined efficacy of vaccination with senescent cells and immunotherapy treatments. Senescent cells have shown promising results as a therapy for cancer, but combining it with immunotherapy treatments could lead to even greater success. Immunotherapy treatments, such as checkpoint inhibitors and CAR-T cell therapy, work by boosting the immune system’s ability to recognize and attack cancer cells.
The IRB Barcelona team is hoping that combining these two therapies will result in a more effective treatment for cancer. “We believe that combining our approach with immunotherapy treatments has the potential to significantly improve the prognosis of cancer patients,” says Dr. Serrano.