Medically reviewed by Dr. Brian Koffman
The Bottom Line:
Inhibiting the pro-inflammatory protein S100A9 impairs chronic lymphocytic leukemia (CLL) growth in a mouse model, decreases CLL-induced immune dysfunction, and improves outcomes.
Who Performed the Research and Where Was it Presented:
Dr. Angimar Uriepero from Moffitt Cancer Center & Research Institute and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2022.
Background:
The tumor microenvironment in the cells, molecules, and blood vessels surrounding the tumor is like the soil surrounding a seed. Like soil affects how a plant grows, the tumor microenvironment can affect how a tumor grows and spreads. Immune cells are part of the tumor microenvironment, and in CLL and small lymphocytic lymphoma (SLL), the immune system is dysregulated paradoxically. On the one hand, patients with CLL / SLL have difficulty responding to vaccines and fighting off infections. On the other hand, there is a lot of inflammation, and immune cells can end up attacking the body’s red blood cells and platelets. The elevated levels of inflammation seen with CLL / SLL can promote tumor growth. Therapies that modulate the inflammatory response can potentially change the tumor microenvironment so that it is less permissive to cancer growth.
In this interview, Dr. Brian Koffman interviewed Dr. Angimar Uriepero, a postdoctoral research fellow at Moffitt Cancer Center in Tampa, FL. They discussed the role of inflammation and the tumor microenvironment in CLL / SLL and how blocking S100A9 with the experimental oral compound, Paquinimod or Tasquinimod, has been studied to treat lupus and COVID-19 inflammation but has significant toxicities.
Methods and Participants:
This research was done in the laboratory with cells in a dish and mice.
Results:
- S100A9 is an upregulated protein in CLL cells and has pro-inflammatory effects.
- Paquinimod inhibits S100A9.
- CLL cells grow more slowly in mice that lack S100A9, and these mice live longer.
- Several experimental drugs that target S100A9 have been tested in clinical trials for other cancers, such as prostate cancer and multiple myeloma.
- CLL is a chronic inflammatory disease that can lead to T-cell exhaustion.
- When mice were treated with the S100A9 inhibitors, Paquinimod or Tasquinimod, CLL proliferation decreased, and T cells were more active with lower expression of exhaustion markers.
- There was a significantly lower amount of CLL in the blood, spleen, and bone marrow in the mice treated with Paquinimod or Tasquinimod compared to the placebo group. They also lived longer, with median survival being 12 weeks in the control group. In the treated group, it was 20 weeks.
- This suggests that cooling the inflammation and improving T-cell functions may lead to better CLL control, at least in mice.
Conclusions:
Inhibiting the pro-inflammatory protein S100A9 with Paquinimod or Tasquinimod impairs CLL growth, decreases CLL-induced immune dysfunction, and leads to better outcomes in a mouse model. Safely and effectively translating these encouraging results from mice to humans is the real challenge.
Links and Resources:
Here you can watch the interview on the full abstract:
Here you can read the actual ASH abstract: Targeting Inflammatory Pathways to Reverse Immunosuppressive Tumor Microenvironment in Chronic Lymphocytic Leukemia
Take care of yourself first.
Ann Liu, PhD
