Evolutionary Mutation Limits Human Immune Response to Solid Tumors, New Study Finds
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- Evolutionary Mutation Limits Human Immune Response to Solid Tumors, New Study Finds
A groundbreaking study from UC Davis Comprehensive Cancer Center reveals an evolutionary quirk that may explain why human immune cells struggle against solid tumors, unlike those in non-human primates. This discovery could pave the way for more potent cancer therapies targeting this vulnerability.
The Evolutionary Trade-Off: Brain Size vs. Cancer Immunity
Published in nature Communications, the research pinpoints a subtle genetic difference in the Fas Ligand (FasL) protein between humans and our primate relatives. This mutation renders human FasL susceptible to inactivation by plasmin, an enzyme associated with tumor growth and spread. This vulnerability appears unique to humans [[SOURCE]].
Did You Know? Humans have a substantially higher rate of cancer than chimpanzees and other primates, suggesting an evolutionary trade-off.
According to Jogender Tushir-Singh, senior author and associate professor at UC Davis, this evolutionary change in FasL might have contributed to the growth of larger brain sizes in humans. However, in the context of cancer, it presents a disadvantage, allowing certain tumors to evade the immune system.
How Tumors Neutralize a Key immune Weapon
FasL, an immune cell membrane protein, is crucial for triggering apoptosis, or programmed cell death, in targeted cells. Activated immune cells, including engineered CAR-T cells, rely on apoptosis to eliminate cancer cells [[REFERENCE]].
The UC Davis team discovered that a single amino acid change-serine rather of proline at position 153-in human FasL makes it more vulnerable to being cleaved and inactivated by plasmin.
Plasmin, a protease enzyme, is frequently enough found in elevated levels in aggressive solid tumors, such as triple-negative breast cancer, colon cancer, and ovarian cancer [[2]].
This means that even when human immune cells are activated and ready to attack,thier primary weapon,FasL,can be neutralized by the tumor habitat,diminishing the effectiveness of immunotherapies.
Implications for Cancer Treatment
These findings may explain why CAR-T and T-cell-based therapies are often effective in treating blood cancers but less so against solid tumors. Blood cancers typically don’t rely on plasmin for metastasis, while tumors like ovarian cancer heavily depend on it [[3]].
potential for Plasmin inhibitors
The study also demonstrated that blocking plasmin or shielding FasL from cleavage can restore its cancer-killing ability. This opens new avenues for enhancing cancer immunotherapy.
By combining existing treatments with plasmin inhibitors or specially designed antibodies that protect FasL,scientists might potentially be able to amplify immune responses in patients with solid tumors.
Pro Tip: Researchers are exploring ways to develop antibodies that specifically target and protect FasL from plasmin cleavage, possibly boosting the effectiveness of immunotherapy.
Comparative Cancer Rates: Humans vs. Primates
| Species | Estimated Lifetime Cancer Risk |
|---|---|
| Humans | 38.4% (United States) [[REFERENCE]] |
| Chimpanzees | Significantly Lower (Specific data varies by study) |
The significantly higher cancer rate in humans compared to primates underscores the importance of understanding these evolutionary differences and their impact on immune responses.
Personalized Immunotherapy on the Horizon
Tushir-Singh emphasizes that this research represents a meaningful step toward personalizing and enhancing immunotherapy for plasmin-positive cancers that have historically been challenging to treat.Further research is needed to fully understand the implications of these findings and translate them into effective clinical strategies.
Understanding Cancer: An Evergreen Perspective
Cancer is a complex disease characterized by the uncontrolled growth and spread of abnormal cells [[1]].It can originate in virtually any part of the body and is influenced by a combination of genetic, environmental, and lifestyle factors. While significant progress has been made in cancer treatment, it remains a leading cause of death worldwide. Understanding the underlying mechanisms of cancer development and immune evasion is crucial for developing more effective therapies.
Frequently Asked Questions About Cancer and Immunotherapy
- What are the most common types of cancer?
- The most common types of cancer include breast cancer, lung cancer, colon and rectal cancer, prostate cancer, and skin cancer [[REFERENCE]].
- What are the main risk factors for developing cancer?
- Major risk factors include tobacco use, unhealthy diet, lack of physical activity, excessive sun exposure, and certain genetic predispositions [[REFERENCE]].
- What are the different types of cancer treatment?
- Common cancer treatments include surgery, chemotherapy, radiation therapy, immunotherapy, targeted therapy, and hormone therapy [[REFERENCE]].
- How does immunotherapy work?
- Immunotherapy boosts the body’s natural defenses to fight cancer. It can involve stimulating the immune system to attack cancer cells directly or using immune system components, such as antibodies, to target cancer cells [[REFERENCE]].
- What is personalized cancer treatment?
- Personalized cancer treatment involves tailoring treatment strategies to an individual’s specific cancer characteristics, including genetic mutations and immune responses. This approach aims to maximize treatment effectiveness while minimizing side effects [[REFERENCE]].
Disclaimer: This article provides general facts about cancer research and treatment. It is not intended to provide medical advice. Consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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