Immune Cell Activity in the Blood Can Predict Tumor Response to Therapy

Killer T-lymphocyte attacking a cancer cell
Killer T-lymphocyte (green) beginning to attack a cancer cell (mauve). Killer T-lymphocytes are part of the body's immune response system.

The types and amounts of circulating immune cells in a patient’s blood can predict whether or not they will respond to cancer therapy, new research from the Translational Genomics Research Institute in collaboration with City of Hope.

People who had a good response to immunotherapy and chemotherapy treatment for advanced gastrointestinal cancer had a rapid increase in tumor-fighting immune cells when their treatment started. This correlated with a reduction in their tumors once the immune cells had reached a certain number. Notably, the team did not see this relationship in patients who did not respond well to therapy.

When the researchers looked at the cells more closely, they found that treatment responders had more anti-tumor T-killer cells and a higher activity of interferon—a protein that has anti-tumor activity—than non responders.

Cancer treatment has improved over the last 20 years, but it has become clearer and clearer that some therapies only work for some patients. For example, immunotherapy has produced amazing results for some advanced stage cancer patients, but still around 40% of people treated with these therapies do not respond.

Better knowledge of biomarkers that can predict whether or not a patient will respond to therapy or not is desperately needed, both to get patients a suitable treatment more quickly and to make sure expensive cancer treatments are not being wasted.

This was the impetus for the study, which was published in the journal PNAS. “We used an ecological population model to understand the interactions between circulating white blood cell abundance and tumor response to immunotherapy,” explained Andrea Bild, PhD, a professor at City of Hope National Medical Center in California and a senior author of the study.

The researchers tested blood samples from gastrointestinal cancer patients enrolled in a clinical trial at the Translational Genomics Research Institute in Arizona, which is affiliated to City of Hope. The researchers took samples before therapy began and at regular intervals during the patient’s treatment with chemotherapy and then combination checkpoint inhibitor immunotherapy and chemotherapy.

At each measurement point, the team looked at amounts of immune cells, such as peripheral blood mononuclear cells and T cells, and tumor cells in the patients’ blood. They also carried out single-cell RNA sequencing to look at the cell characteristics more closely.

“The study shows that subsets of immune cells in the blood indicate how each cancer patient responded to this combination of chemotherapy and immunotherapy,” said Sunil Sharma, MD, Deputy Director of Clinical Services at the Translational Genomics Research Institute, who is also a senior author of the study.

“We found, using this combination drug approach, that the body’s own immune response and its activation correlated with a higher response to the therapy among cancer patients.”

In this study the researchers were looking more generally at the response of circulating immune cells to cancer therapies, but in future they hope to narrow this down and work out which response corresponds to treatment with different drugs or therapies.

“We believe there is potential to measure a tumor’s response to specific drugs using circulating immune cell dynamics, which are accessible and collected from a blood draw,” said Bild.

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