Innovative vaccine significantly reduces the risk of skin and pancreatic cancer

Vaccination with senescent cells significantly reduces tumor development in experimental models of melanoma and pancreatic cancer. (CREDIT: Creative Commons)

Researchers at IRB Barcelona report that the induction of tumor cell senescence strongly stimulates the immune system.

Vaccination with senescent cells significantly reduces tumor development in experimental models of melanoma and pancreatic cancer.

The study is published in the journal Cancer Discovery.

Cancer cells have a number of features that allow the immune system to identify and attack them. However, these same cells create an environment that blocks immune cells and protects the tumor. This means that the immune cells cannot get to the cancer cells to remove them. The scientific community has been working for many years to improve the effectiveness of the immune system against cancer with vaccines based on dead tumor cells.

IRB Barcelona scientists, led by ICREA researcher Dr. Manuel Serrano and Dr. Federico Pietrocol from the Karolinska Institute in Sweden, have studied how inducing cancer cell senescence increases the efficiency of the immune response to a greater extent. than dead cancer cells.

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After inoculating healthy mice with aging cancer cells and then stimulating tumor formation, the researchers noticed that the animals did not develop cancer or that the number of cases dropped significantly. They also analyzed the efficacy of vaccinating animals that had already developed tumors. In this case, although the results were more moderate due to the protective barrier of the tumor, improvements were also observed.

“Our results show that senescent cells are the preferred option when it comes to stimulating the immune system against cancer, and they pave the way for considering vaccination using these cells as a possible therapy,” explains Dr. Serrano, Head of Cellular Plasticity and Laboratory diseases IRB in Barcelona.

The researchers tested the method in animal models of melanoma, a type of cancer characterized by highly activated immune systems, as well as models of pancreatic cancer, which present strong barriers against immune cells. Prophylactic vaccine 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 ability to activate the immune system when they age earlier.

Immune cell infiltrate (in dark red) around aging cancer cells (large nuclei in blue). (PREDICTION: IRB Barcelona)

The group is currently investigating the combined efficacy of senescent cell vaccination and immunotherapy treatments.

Aging and its ability to activate the immune system

Aging is a latent state reached by damaged or aged cells, in which they do not multiply, but do not disappear either. Senescent cells emit information signals to the environment that alert them to their presence, stimulating an inflammatory response and tissue regeneration.

Aging tumor cells, mouse pancreatic cancer cell culture. (PREDICTION: IRB Barcelona)

In the context of cancer, researchers led by Dr. Serrano found that senescent cells, due to their characteristics, are a good option for activating the immune system and improving its response to a tumor.

On the one hand, because senescent cells are living cells, they stay in the body longer than dead cells and are therefore able to stimulate the immune system longer. On the other hand, since these cells do not divide, they cannot regenerate the tumor.

“Our study concluded that induction of tumor cell senescence improves the recognition of these cells by the immune system and also increases the intensity of the response they generate. Thus, our results are very positive,” explains Ines Marin, a doctoral candidate from the same laboratory and the first author of the study.

The researchers tested the method in animal models of melanoma, a type of cancer characterized by highly activated immune systems, as well as models of pancreatic cancer, which present strong barriers against immune cells. (PREDICTION: IRB Barcelona)

As observed in this study, senescent cells present unique signals that stimulate recognition and activation of the immune system, and which differ from the signals presented by cells prior to senescence induction.

Parallel discovery made by Dr. Scott W. Lowe and Dr. Direna Alonso-Curbelo.

The discovery, made by the Cellular Plasticity and Disease Laboratory, was published simultaneously and in the same journal as another paper prepared by the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and completed in collaboration with IRB Barcelona.

The latter, sponsored by Dr. Direna Alonso-Curbello, now head of the Inflammation, Tissue Plasticity and Cancer Laboratory at the IRB in Barcelona, ​​and Dr. Scott W. Lowe, come to additional conclusions despite studying the subject with a very different approach.

In short, the work started at MSKCC has focused on describing how the induction of tumor cell senescence alters the molecular programs that mediate communication between the tumor and the immune system. “Until now, most research has focused on the ability of senescent cells to send inflammatory signals to the environment. Our work shows that this relationship is bidirectional, showing that aging increases the ability of cells to “receive” signals from the environment that activate key pathways for their recognition and destruction by cytotoxic T cells,” explains Dr. Alonso-Curbelo.

This work demonstrates that the ability to “receive” signals from the environment, which is increased by the induction of aging, enhances the antitumor effect of signals such as interferon, making tumor cells more visible to the immune system and reactivating the antitumor effect. Immunity in liver cancer models.

Other diseases associated with aging and those dominated by the presence of senescent cells, such as atherosclerosis, may also benefit from potential senescent cell vaccines. In this regard, IRB Barcelona scientists also report that senescent cells can be mistakenly recognized by immune cells as if they were foreign cells. These results are consistent with the findings of other researchers working with stressed cells, which can also be mistaken for foreign cells.

The study, led by IRB Barcelona, ​​was carried out in collaboration with laboratories led by Dr. Maria Abad and Dr. Alena Gros at the Val d’Hebron Oncology Institute (VHIO) in Barcelona and Dr. Etienne Caron at CHU Sainte. – Justine Research Center in Canada. In addition, the Biostatistics and Bioinformatics Department under the direction of Dr. Camilla Stephan-Otto Attolini and the main Histopathology Center under the direction of Dr. Neus Prats also participated in the IRB in Barcelona.

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Note: Materials provided above by the Institute for Biomedical Research. Content can be edited for style and length.

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