Aging is a well-known risk factor for cancer, but how exactly it influences the body’s ability to control tumors has been somewhat unclear. Recent findings reveal that it’s not just the age of the tissue or tumor that matters; rather, it’s the aging of the immune system that drives cancer progression, particularly in lung cancer.
As the immune system ages, it undergoes changes that lead to emergency myelopoiesis, a process where the body produces more myeloid cells (a type of immune cell) in response to tumors. This results in the local buildup of myeloid progenitor-like cells in the lungs, which play a significant role in promoting tumor growth. These cells are also a major source of IL-1⍺, a molecule that enhances the myeloid response and accelerates cancer progression.
A key factor in this process is the age-related decline of DNMT3A, an enzyme that helps regulate immune responses. As DNMT3A levels decrease with age, IL-1⍺ production increases, further driving cancer development. However, there is hope: research has shown that by blocking IL-1R1 signaling (a pathway that responds to IL-1⍺) early in tumor development, it is possible to normalize the immune response and slow down the growth of cancers, including lung, colon, and pancreatic tumors.
Human studies have also found that older patients with tumors show an increase in IL-1⍺-producing macrophages, a type of immune cell linked to worse survival rates and a higher likelihood of recurrence. This discovery highlights how aging contributes to cancer progression and opens up new avenues for therapeutic strategies aimed at targeting these age-related immune changes.
In summary, while aging is a natural process, its impact on the immune system can significantly affect cancer outcomes. By better understanding the mechanisms at play, such as IL-1⍺ production and immune cell behavior, researchers are uncovering potential treatments that could improve survival and reduce cancer recurrence, especially in older populations.
Reference: Matthew D. Park, Jessica Le Berichel, Pauline Hamon, C. Matthias Wilk, Meriem Belabed, Nader Yatim, Alexis Saffon, Jesse Boumelha, Chiara Falcomatà, Alexander Tepper, Samarth Hegde, Raphaël Mattiuz, Brian Y. Soong, Nelson M. LaMarche, Frederika Rentzeperis, Leanna Troncoso, Laszlo Halasz, Clotilde Hennequin, Theodore Chin, Earnest P. Chen, Amanda M. Reid, Matthew Su, Ashley Reid Cahn, Laura L. Koekkoek, Nicholas Venturini, Shira Wood-isenberg, Darwin D’souza, Rachel Chen, Travis Dawson, Kai Nie, Zhihong Chen, Seunghee Kim-Schulze, Maria Casanova-Acebes, Filip K. Swirski, Julian Downward, Nicolas Vabret, Brian D. Brown, Thomas U. Marron, Miriam Merad. (5 Sep 2024). Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis. Science (New York, N.Y.). https://doi.org/10.1126/science.adn0327
