Cancer Mutation: Immune System Escape
- A new study from UC Davis Extensive Cancer Center reveals an evolutionary quirk that may explain why human immune cells struggle against solid tumors, a challenge not seen...
- Published in Nature Communications, the research pinpoints a subtle genetic variation in the Fas Ligand (FasL) protein.This mutation renders human FasL susceptible to deactivation by plasmin, an enzyme...
- Jogender Tushir-Singh,an associate professor at UC Davis,led the study.He suggested the FasL mutation might have played a role in the advancement of larger human brains.
UC Davis researchers have uncovered a critical genetic difference that hinders cancer immunotherapy in humans. The study reveals a vulnerability in the FasL protein,a vital component of immune cells,rendering it susceptible to deactivation by plasmin,an enzyme prevalent in solid tumors. This cancer mutation, not shared by primates, possibly explains why immunotherapy is less effective against solid tumors. Blocking plasmin or safeguarding FasL could restore the cancer-fighting capabilities of immune cells, offering a promising path to enhance existing treatments.This research could lead to new strategies to fight the disease! For more updates, consider checking out News Directory 3. Discover whatS next in immunotherapy advancements and the potential to improve patient outcomes.
Evolutionary Change May Improve Cancer Immunotherapy
Updated july 3, 2025
A new study from UC Davis Extensive Cancer Center reveals an evolutionary quirk that may explain why human immune cells struggle against solid tumors, a challenge not seen in non-human primates. the finding offers a potential path to more effective cancer treatments, notably in the realm of immunotherapy.
Published in Nature Communications, the research pinpoints a subtle genetic variation in the Fas Ligand (FasL) protein.This mutation renders human FasL susceptible to deactivation by plasmin, an enzyme often associated with tumors.Chimpanzees and other primates do not share this vulnerability.
Jogender Tushir-Singh,an associate professor at UC Davis,led the study.He suggested the FasL mutation might have played a role in the advancement of larger human brains. However, he noted a downside: “In the context of cancer, it was an unfavorable tradeoff because the mutation gives certain tumors a way to disarm parts of our immune system.”
FasL, a protein on immune cell membranes, triggers apoptosis, a programmed cell death. Activated immune cells, including engineered CAR-T cells, use this process to eliminate cancer cells.
the UC Davis team discovered that a single amino acid change-serine instead of proline at position 153-in human genes makes FasL vulnerable to plasmin. This protease enzyme is often elevated in aggressive solid tumors, such as triple-negative breast cancer, colon cancer, and ovarian cancer.
This means that even when human immune cells are activated to fight cancer, their primary weapon, FasL, can be neutralized by the tumor’s surroundings. This reduces the effectiveness of immunotherapies.
The findings may explain why CAR-T and T-cell therapies are more successful in treating blood cancers than solid tumors. Blood cancers typically do not rely on plasmin for metastasis, while tumors like ovarian cancer depend heavily on it to spread.
The study also demonstrated that blocking plasmin or protecting FasL can restore its cancer-killing ability. This could lead to new strategies for enhancing cancer immunotherapy.
Scientists believe that combining existing treatments with plasmin inhibitors or antibodies that shield FasL could boost immune responses in patients with solid tumors.
“Humans have a significantly higher rate of cancer than chimpanzees and other primates,” Tushir-Singh said. “There is a lot that we do not know and can still learn from primates and apply to improve human cancer immunotherapies.” He added that this research represents “a major step toward personalizing and enhancing immunotherapy for the plasmin-positive cancers that have been tough to treat.”
What’s next
Researchers plan to explore how plasmin inhibitors and FasL-shielding antibodies can be integrated into existing cancer treatment protocols to improve patient outcomes,particularly for those with solid tumors.