Why Have My Natural Killer Cells Stopped Killing CLL Cells?

What are natural killer cells? Why do they stop killing chronic lymphocytic leukemia (CLL) cells? What can potentially fix this? Learn answers to these questions below! 

Can Natural Killer Cells Kill CLL? 

Natural killer (NK) cells are part of your immune system. After recognizing cancer cells as abnormal, they release toxic molecules that cause cancer cells to self-destruct. 

PhD researcher Sigrid S. Skånland of the Oslo University Hospital in Norway found that after CLL patients achieved remission following venetoclax (Venclexta, AbbVie) treatment, the new CLL cells that tried to arise were killed off by patients’ own natural killer cells. 

After a period of time, the natural killer cells became exhausted, causing the CLL cells to increase again, leading to patients relapsing. Had the NK cells not become exhausted, they would have continued to kill new CLL cells, potentially keeping patients in long-term remission. 

What Causes Natural Killer Cell Exhaustion? 

Santosha Vardhaha, MD, PhD, from Memorial Sloan Kettering Cancer Center (MSK) found that immune system cell exhaustion is caused by an increase in oxidative stress and is reversible with antioxidant treatment. 

Oxidative stress refers to the imbalance of excess free radicals and insufficient antioxidants. High amounts of free radicals can damage parts of the cell, like the mitochondria. As mitochondria are in charge of providing energy to the cell, damage caused by free radical buildup over time causes cellular exhaustion and fatigue. 

Dr. Vardhaha found that when antioxidants were administered, the cell’s mitochondria reversed the damage and kept functioning, helping immune system cells continue killing cancer cells and avoiding exhaustion. 

Click here to learn more about sources that cause oxidative stress and ways you can reduce it. 

MSK is now implementing Dr. Vardhaha’s research combining antioxidants alongside CAR T-cell therapy into a clinical trial for high-risk lymphoma patients (click here to read more). We hope that similar treatment strategies are implemented for people with CLL. 

Can I Reverse My Own NK Cell Exhaustion? 

It may be safest for the administration of antioxidant therapy to be conducted in clinical trials supervised by doctors. This is because antioxidants de-exhaust all cells, including cancer cells. Certain cancer cells’ DNA is genetically altered, either by a virus or other means, to have powerful mitochondria that work well despite an environment of high oxidative stress. This accounts for why cancer cells often advance when other immune system cells become fatigued. 

Research needs to be conducted to evaluate if patients have enough cancer-killing immune system cells like NK cells and T cells before increasing antioxidants, giving empowerment to the right immune system cells (not only decreasing all-over cellular exhaustion with antioxidants, thus allowing cancer cells to rapidly increase and hope that patients own NK cells and T cells can catch up in time). 

To overcome this obstacle, it may be safe to increase your consumption of foods/spices high in antioxidants once in remission following standard CLL treatment or in combination with a treatment that increases immune system cells, like CAR NK-cell therapy or CAR T-cell therapy. 

Conclusion

In summary, natural killer (NK) cells are crucial parts of the immune system and have the power to kill CLL cells. However, over time, NK cells become exhausted, which is caused by oxidative stress. Thankfully, this exhaustion is reversible by using antioxidants, as shown by Dr. Vardhaha's research. Further research can help identify the best way to use antioxidants in treatment without accidentally helping cancer cells grow. Encouraging patients to consume more foods/spices high in antioxidants once they achieve remission following a standard CLL therapy or combining antioxidants with immune system-boosting treatments like CAR T-cell therapy may be promising. These strategies could lead to managing CLL more effectively and improving how the immune system responds in patients, which is a step towards prolonging long-lasting remissions.  

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Sources: 

• Functional Testing of Relapsed Chronic Lymphocytic Leukemia Guides Precision Medicine and Maps Response and Resistance Mechanisms. An Index Case

• Study Shows How Immune Cells Lose Their Power to Fight Tumors

• Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis