Early activation of programmed cell death-1 (PD-1) in CD8 T-cells after immunotherapy treatment is crucial to anti-tumor response for patients with non-small cell lung cancer (NSCLC), according to research published in Proceedings of the National Academy of Sciences (published online April 26, 2017; doi:10.1073/pnas.1705327114).
Therapies that inhibit the PD-1 pathway have demonstrated clinical benefit in multiple trials for patients with advanced-stage cancer. However, a further understanding of the immunological responses from PD-1 inhibition – and identification of biomarkers – is lacking. Research to determine whether peripheral blood analysis can provide biomarkers to monitor or predict patient response to immunotherapy treatment is needed.
Rafi Ahmed, PhD, Emory Vaccine Center (Georgia), and colleagues analyzed changes in peripheral blood T-cells from patients with NSCLC who received PD-1 targeted therapies. A total of 29 patients underwent blood samples before starting treatment and before each new treatment cycle, which lasted 2 to 3 weeks.
Researchers found that approximately 70% of patients exhibited an increase in CD8 T-cells after treatment. Only some patients showed a partial clinical response, defined as a tumor burden reduction of greater than or equal to 30%. All of the patients with partial responses survived at least 1 year, while only an estimated 14% of patients with progressive disease survived 1 year.
A detailed analysis of each patient showed that increase in activated PD-1 positive CD8 T-cells correlated with response to treatment. Eighty percent of patients with clinical benefit demonstrated PD-1 positive T-cell response within 4 weeks of beginning treatment, whereas 70% of patients who did not respond to treatment showed absent PD-1 positive CD8 T-cell responses.
Implications of these findings suggest that activation of PD-1 expression in CD8 T-cells within 4 weeks from immunotherapy treatment initiation is essential to anti-tumor response for patients with NSCLC. Though not a prognostic tool, monitoring activated CD8 T-cells can aid physicians and patients with immunotherapy decision-making.
“Our ability to detect proliferating T-cells in the blood and correlate this with clinical benefit is exciting, since this captures a real-time assessment of the immune system’s response to PD-1 directed therapies and is a readily accessible test from our patients’ perspective,” said Rathi Pillai, MD, author of the study, in a press release (April 24, 2017).
Further research is being conducted to confirm these results and to assess the predictive abilities of CD8 T-cells in multiple cancer types. – Zachary Bessette