Vaccinating with senescent cells can significantly reduce the development of tumors

• Researchers at IRB Barcelona report that inducing aging of tumor cells strongly stimulates the immune system
  .
  

• In experimental models of melanoma and pancreatic cancer, vaccination with senescent cells significantly reduced tumor development
  .
  

• The study has been published in the journal Cancer Findings.
  

Cancer cells have a range of characteristics that allow the immune system to recognize and attack them
.
However, these same cells create an environment that blocks immune cells and protects tumors
.
This means that immune cells cannot reach cancer cells to clear them
.
For years, the scientific community has worked to improve the effectiveness
of the immune system against cancer by using vaccines based on dead tumor cells.

Scientists at IRB Barcelona, led by ICREA researcher Dr.
Manuel Serrano and Dr.
Federico Pietrocola, now at the Karolinska Institutet in Sweden, have studied how inducing aging in cancer cells can increase the effectiveness of the immune response to a greater extent
than dead cancer cells.
After vaccinating healthy mice with senescent cancer cells and then stimulating tumor formation, the researchers observed that the animals did not develop cancer and that the number of cancers was significantly reduced
.
They also analyzed the effects of
vaccination on animals that had already developed tumors.
In this case, although the results are milder due to the protective barrier of the tumor, improvement
is also observed.

Dr Serrano, Director of the Laboratory of IRB Cell Plasticity and Disease in Barcelona, explains: "Our findings suggest that senescent cells are the preferred option to stimulate the immune system to fight cancer, and they pave the way for
consideration of vaccination with these cells as a possible treatment.
"

The researchers tested the technique in animal models of melanoma, a cancer characterized by a highly activated immune system, and in models of pancreatic cancer, which creates a powerful barrier
to immune cells.
Prophylactic vaccination treatment for senescent cancer cells is effective
for both types of tumors.
They also supplemented their research with tumor samples from cancer patients and confirmed that human cancer cells also have a greater ability to activate the immune system
when they were previously rendered to be senescent.

The team is currently studying the combined effects
of immunization with senescent cells and immunotherapy.

Aging and its ability to activate the immune system

Senescence is a delayed state reached by damaged or senescent cells in which they neither multiply nor disappear.

Senescent cells send information signals to their surroundings, warning of their presence, stimulating the inflammatory response and tissue regeneration
.

In the field of cancer, researchers led by Dr.
Serrano have found that due to the properties of senescent cells, they are a good choice
for activating the immune system and improving their response to tumors.
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
for a longer period of time.
On the other hand, because these cells do not divide, they cannot regenerate tumors
.

"Our study concluded that inducing senescence in tumor cells improves the immune system's ability to recognize these cells and also increases the intensity
of the responses they produce.
" So our findings are very positive," explains
Inés Marín, a PhD student from the same lab and first author of the study.

In this study, it was observed that senescent cells exhibit unique signals that are recognized by activation and stimulation by the immune system, unlike those presented by cells before induction of senescence
.

A parallel find

In short, MSKCC's work began by describing how aging, inducing tumor cell senescence alters the molecular program
that mediates communication between tumors and the immune system.
So far, most research has focused on the
ability of senescent cells to "send" inflammatory signals to their surroundings.
Our study shows that this communication is bidirectional, revealing that senescence increases the ability of cells to 'receive' signals from the environment, activating a key pathway for cytotoxic T cells to recognize and destroy them," explains Dr.
Alonso-Curbelo
.

This study shows that the enhanced ability to "receive" environmental signals by inducing aging amplifies the anti-tumor effects of signals such as interferon, makes it easier for the immune system to see tumor cells, and reactivates anti-tumor immunity
in liver cancer models.

Other aging-related diseases and diseases prevalent in senescent cells, such as atherosclerosis, can also benefit
from vaccines that contain senescent cells.
In this regard, scientists at IRB Barcelona also report that senescent cells may be misrecognized by immune cells as if they were foreign
.
The findings are consistent with those reported by researchers who study cells under stress, which can also be mistaken for foreign cells
.