U of A study identifies why immunotherapy isn’t effective for many cancer patients

Shokrollah Elahi

A new University of Alberta study has identified why some cancer patients don’t respond to immunotherapy treatment, potentially paving the way for new and more effective treatments.

Immunotherapy has revolutionized the field of cancer treatment by improving the immune system’s ability to detect and fight cancer cells. 

However, the treatment is not effective for everyone. Only 15 to 20 per cent of cancer patients respond to immunotherapy drugs.

“It’s a major question in the field,” says immunologist and lead researcher Shokrollah Elahi. “Why don’t some patients respond to these drugs the way others do? If we can understand why, we should be able to develop treatments that benefit these non-responding patients.”

Looking for an answer, Elahi and his team studied cancer patients receiving immunotherapy treatment at the Cross Cancer Institute over two years. They identified which patients responded to the treatment and which did not. 

Through analysis, they discovered the non-responding patients had much higher levels of immature red blood cells — also known as CD71+ erythroid cells or CECs — in their blood circulation.

How were these elevated levels of CECs associated with being non-responsive to immunotherapy?

Elahi and his team performed extensive studies on the immunological properties of these immature red blood cells. They observed that they have immunosuppressive properties that prevent the immune system from eliminating cancer cells.

Additional investigations showed that anemia — a condition often found in late-stage cancer patients, in which the body does not have enough healthy red blood cells — was the cause of elevated levels of CECs in non-responding patients. 

One of the commonly prescribed treatments for anemia is erythropoietin (EPO). While EPO helps the production of red blood cells in patients with anemia, one side-effect is increased levels of CECs as well.

“Some cancer patients with anemia are also being given EPO, which increases their immature red blood cell levels, which then lowers their immune system’s ability to fight cancer cells,” says Elahi.

“Overall, our results show that chronic anemia elevates CEC levels, which weakens the immune system against cancer cells. We also noted that CECs were significantly higher at the baseline and throughout the study in non-responders, so measuring CECs in the blood may serve as a valuable and non-invasive prognostic biomarker to predict immunotherapy outcomes,” adds Elahi.

Study results showed that female cancer patients were more likely to experience anemia and have more CECs than males.

Larger studies are now needed to validate these findings.

“Taken together, our results shed light on the adverse effects of chronic anemia on both cancer progression and immunotherapy outcomes,” says Elahi. “Management of chronic anemia should be considered a priority in cancer patients.” 

“Looking ahead, therapies that prevent elevated immature red blood cell levels or block their immunosuppressive properties could be explored as new approaches in cancer treatment.”

Shokrollah Elahi is a member of the Cancer Research Institute of Northern Alberta and the Women and Children's Health Research Institute.