Blood Analysis May Predict Responses to PD-1-Targeted Therapies in Lung Cancer

Peripheral blood analysis may provide valuable insights into non–small-cell lung cancer (NSCLC) patients’ responses to programmed cell death 1 (PD-1)-targeted therapies, according to researchers at Emory University. They have published a study in the journal Proceedings of the National Academy of Sciences of the United States of America that demonstrated clinicians may be able to capture a real-time assessment of the immune system’s response to PD-1 directed therapies.

The researchers found that if CD8 T cells in lung cancer patients appeared to respond to immunotherapy it was a good sign. The authors suggest the findings may have significant clinical implications. Using this simple monitoring approach could help clinicians and patients decide within just a few weeks of starting an immunotherapy whether to continue with current treatment or combine it with something else.

The researchers examined blood samples from 29 advanced NSCLC patients undergoing immunotherapy. The patients were being treated with checkpoint inhibitors (nivolumab, pembrolizumab, or atezolizumab). Blood samples were obtained before starting treatment and before each new treatment cycle, which lasted 2 to 3 weeks.

The team found that an early increase in activated PD-1-positive CD8 T cells was predictive. The researchers found that 80% of patients with clinical benefit exhibited PD-1-positive CD8 T cell responses within 4 weeks of treatment initiation. In contrast, 70% of patients with disease progression had either delayed or absent PD-1-positive CD8 T cell responses.

"We hypothesize that reactivated CD8 T cells first proliferate in the lymph nodes, then transition through the blood and migrate to the inflamed tissue," said co-senior author Rafi Ahmed, PhD, who is the director of The Emory Vaccine Center in Atlanta. "We believe some of the activated T cells in patients' blood may be on their way to the tumor."

Most patients (70%) displayed an increase in the number of proliferating CD8 T cells in their blood after starting PD-1 targeted treatment. However, not all patients with an immunological response experienced a partial clinical response (tumors shrank by at least 30%). All the patients with partial responses survived at least 1 year. Only one of seven patients with progressive disease was reported to survive 1 year. Survival times for three patients were not available.

Detecting treatment failures on immunotherapy earlier rather than later could significantly improve outcomes. Peripheral blood analyses are easy to perform and can be repeated at several time points and may be highly beneficial, note the authors. 

In this study, proliferating CD8 T cells displayed high levels of PD-1, as well as other molecules that influence their activity, which may be targets for combination therapies. The Emory team is already undertaking a larger study to confirm these initial findings and it is extending investigations into other tumor types.