NK cells stopped Killing CLL cells because of exhaustion

In a CLL study led by PhD researcher Sigrid S. Skånland, one of the facts she and her team from the Oslo University Hospital in Norway came across was how the patient’s cancer-killing immune system cells (natural killer (NK) cells) behaved after the patient was placed into remission following venetoclax treatment.  

Once in remission after venetoclax treatment, the research team found that the CLL patient’s own NK cells were killing new CLL cells that tried to multiply. The NK cells stopped killing new CLL cells when the NK cells became exhausted, thus allowing the CLL cells to increase again. Had the patient's NK cells not become exhausted, they would have kept killing CLL cells and kept the patient in remission. 

Immune system cell exhaustion caused by excess oxidative stress and reversed with antioxidants 

Santosha Vardhaha MD, PhD, and his team with the Memorial Sloan Kettering Cancer Center in New York City found that the reason cancer-killing immune system cells (like NK cells) get exhausted is because excess oxidative stress builds up in the cell’s mitochondria as it attacks a cancer cell. 

Over time, the oxidative stress becomes too much and the immune system cell’s mitochondria become “exhausted”, stopping the cell from working to kill cancer cells or multiply. 

The amount of excess oxidative stress in the body is also influenced by the intake of high oxidative stress causing environmental substances found here (like herbicides, refined sugar, meats cured with nitrates, etc).

Dr. Vardhaha found that this cellular exhaustion is reversible by administering antioxidants. After increasing antioxidants, the cancer-killing immune system cells’ fatigue were reversed and they were able to continue killing cancer cells as well as multiplying to circulate the body.

MSK is now implementing Dr. Vardhaha’s research into a clinical trial for high-risk lymphoma patients (read more here). We hope to implement similar treatment strategies through clinical trials for CLL patients. 

See here for a list of high-antioxidant foods and spices patients can include in their meals. 

Next Steps 

Through clinical trials with the support of doctors, researchers, fund donors, and CLL patients, we can help implement these facts into treatment action for patients. 

Further research is needed to review items such as helping ensure a CLL patient already has enough NK cells to empower with antioxidants, or if multiplying the NK cells in a lab and then infusing them into the patient in combination with antioxidants is needed to kill CLL cells. Clinical trials will also help determine the appropriate dose of antioxidants needed to reverse NK cell fatigue. 

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