Chronic lymphocytic leukemia (CLL) severely impairs normal immune system function, which leads to increased risk of infections and secondary cancers. Chemotherapy, a key component of some treatment regimens, further weakens the immune system and can increase susceptibility to infections.
Restoring immune system function is key for long-term health and survival, but the immune system is incredibly complex and is made up of a multitude of different types of cells and proteins. So where do we begin?
Malignant CLL B cells have evolved strategies for evading or suppressing the immune system, especially the anticancer effects of T cells. CLL changes the types of T cells present in the body and produces abnormalities in how they function.
Regulatory T cells normally control the immune response to self and foreign particles, and they prevent other T cells from overreacting and potentially causing autoimmune reactions. However, in CLL there is an increased number of regulatory T cells, and they eventually suppress the body’s ability to recognize and kill cancer cells.
At the annual meeting of the American Society of Hematology (ASH) 2019, Dr. John Pagel, MD, PhD, interviewed Dr. Alexey Danilov, MD, PhD, Associate Director of the Toni Stephenson Lymphoma Center at City of Hope in Duarte, CA. They discussed the role of T cells and targeted therapies in modulating immune function in CLL.
Takeaways:
- Patients with CLL are susceptible to infections and secondary cancers because their immune system is not functioning at 100%.
- Specifically, the T cells in CLL patients are “exhausted” and don’t respond to bugs as well as in normal individuals.
- Danilov and his team are studying whether some immune function can be restored by using the preclinical agent pevonedistat, which targets the protein turnover process.
- In cell culture, pevonedistat was able to restore some T cell functionality, which could potentially increase the ability of T cells to kill microbes.
- In a mouse model, pevonedistat reduced the number of regulatory T cells, which supports the cell culture data showing improvements in T cell functionality.
Conclusions:
The vulnerability of the immune system is a major concern for patients with CLL since preventing infections and secondary cancers is critical to long-term health. While chemotherapy regimens further weaken the immune system, newer targeted agents may actually have some beneficial effects on the immune response. Right now, we don’t fully understand what those effects are, but research such as this is helping us to understand a very complex system.
Please enjoy this brief interview with Dr. Danilov from December 2019 at ASH in Orlando, FL presenting a novel approach to improving the immune system.
You can read the abstract here: Neddylation Pathway Regulates Treg Differentiation and T Cell Function in Chronic Lymphocytic Leukemia (CLL) Ex Vivo and Murine In Vivo Studies
See our previous interview with Dr. Adrian Wiestner for more information about how BTK inhibitors ibrutinib and acalabrutinib affect immune function.
Take care of yourself first.
Ann Liu, PhD
