Uncategorized Thursday, 2024/10/17
Researchers from the Icahn School of Medicine at Mount Sinai have published a research paper titled "Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis" in the top international academic journal Science.
This study suggests that regardless of the age of the matrix and tumor, the aging of the immune system can produce harmful inflammatory responses, thereby promoting cancer development. Blocking the inflammatory pathway (IL-1 ⍺/IL-1 β) can reverse the pro-cancer effects of aging, opening up new avenues for cancer prevention.
This study provides strong evidence for the first time that chronic inflammation caused by an aging immune system can easily lead to cancer. Based on these findings, the research team has initiated an early clinical trial to validate whether targeting the aging immune system with anakinins (IL-1R1 antagonists commonly used to treat inflammatory diseases such as rheumatoid arthritis) can prevent cancer progression.
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| IL1A-01H | Recombinant Human IL1A protein | E.coli | Human | Non | 159 | |
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| IL1B-744H | Active Recombinant Human IL1B protein(Met1-Ser269), His-tagged | E.coli | Human | His | Met1-Ser269 | |
| DNMT3A-12110H | Recombinant Human DNMT3A, GST-tagged | E.coli | Human | GST | 1-280a.a. | |
| IL1A-14166H | Recombinant Human IL1A, GST-tagged | E.coli | Human | GST | 1-271a.a. | |
| IL1B-14167H | Recombinant Human IL1B protein, GST-tagged | E.coli | Human | GST | 1-269 aa | |
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The corresponding author of the paper, Professor Miriam Merad, stated that this study found that by blocking specific inflammatory pathways (especially those involving IL-1 ⍺/IL-1 β), the promotion of cancer by the aging immune system can be reversed, providing a potential new method for preventing the development of human cancer.
In this latest study, the research team is dedicated to answering an important but yet-to-be-fully-explored question in cancer research - why is aging the biggest risk factor for cancer?
The research team used a mouse model to study how aging affects cancer progression. They injected tumor cells into mice and observed that lung cancer, pancreatic cancer, and colon cancer in aging mice grew faster than in young mice. Then, the research team used bone marrow transplants from young or aging mice to simulate the effects of immune system aging. It was found that the aging immune system accelerated cancer growth, even in young mice. More notably, restoring the immune system to youthfulness can significantly reduce cancer growth in aging mice.
Specifically, IL-1 ⍺ derived from bone marrow progenitor cell-like cells is a key driving factor for the acute bone marrow cell generation response that promotes aging enhancement, and this acute bone marrow cell generation response promotes immune suppression. In the early stages of tumor development, blocking this signaling axis with anti-IL-1 ⍺ antibodies can not only slow down tumor growth, but also normalize acute bone marrow cell production in aging mice. In addition, blocking IL-1 β can also help reduce tumor progression, but the combination of blocking IL-1 ⍺/IL-1 β or using Anakinra (IL-1R1 antagonist) can most effectively block tumor initiation.
Next, the research team determined that hematopoietic aging enhances the production of IL-1 ⍺ and IL-1 β by downregulating DNA methyltransferase 3A (DNMT3A). The research team further examined primary tissue and blood samples from human lung cancer patients, demonstrating the conservation of these mechanisms in human myeloid cells. The enrichment of macrophages derived from monocytes expressing IL-1 ⍺ was associated with age, poor survival rates, and tumor recurrence.
The first author of the paper, Dr. Matthew D. Park, stated that as the immune system ages, it triggers harmful inflammation that drives cancer growth by promoting the accumulation of tumor-promoting macrophages (immune cells that inhibit the killing of tumors). Tumor-promoting macrophages weaken the body's ability to fight cancer by inhibiting immune effector cells that kill tumors.
The corresponding author of the paper, Professor Miriam Merad, stated that the aging immune system promotes cancer progression, which is independent of the age of cancer cells or surrounding tissues. They have always suspected that inflammation can suppress anti-tumor immunity, especially in the elderly and cancer patients. This study provides strong evidence for the first time that chronic inflammation caused by an aging immune system can easily lead to cancer. This study not only provides us with a new understanding of immune aging, but also lays the foundation for future research, including exploring the relationship between immune aging and cancer and other aging-related diseases such as cardiovascular disease and infections.
Overall, this study suggests that targeting the aging immune system can significantly reduce the risk of cancer in older adults, suggesting that enhancing immune response through immunotherapy may be more effective than directly targeting tumors.
Anakinra is a recombinant human IL-1 receptor antagonist that can block the activity of IL-1 ⍺ and IL-1 β. It is commonly used to treat inflammatory diseases such as rheumatoid arthritis. This study suggests that anakinins can alleviate the harmful effects of immune aging on cancer, opening the door to reusing existing drugs for cancer prevention.
It is reported that the research team has designed an early clinical trial of anakinins for high-risk cancer patients based on this research discovery. This ongoing clinical trial is investigating whether targeting the aging immune system can prevent cancer progression, while the research team continues to explore other therapeutic targets. Their ultimate goal is to develop preventive measures to reduce harmful inflammation in the elderly, thereby significantly reducing the incidence rate of cancer.
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Reference
Park MD, Le Berichel J, Hamon P, et al. Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis. Science. 2024 Sep 5:eadn0327. doi: 10.1126/science.adn0327. Epub ahead of print. PMID: 39236155.