Abstract
Recent success of using agents inhibiting the major immune check point, programmed cell death-1 (PD-1) pathway, offers a great promise for effective cancer therapy. Two blocking antibodies for PD-1, nivolumab and pembrolizumab have recently been approved for treating advanced recurrent non-small cell lung cancer (NSCLC). Activation of PD-1 on T cells and PD-L1 on tumor cells or antigen presenting cells leads to T cell exhaustion and ultimately tumor growth. In this study, we performed flow cytometry analysis of peripheral blood samples collected from patients with advanced NSCLC at initial diagnosis. We report that surface expression of PD-1 on CD4+ T cells has a prognostic value in NSCLC patients, as high expression of PD-1 is associated with a shorter progression-free survival and overall survival. Importantly, we also found that high PD-1 expression on peripheral CD4+ T cells is associated with inferior clinical response in a subset of patients who received anti-PD-L1 treatment, indicating a potential predictive value of this marker. This work highlights the potential of a non-invasive and effective method to determine prognostic and predictive biomarkers for inhibiting the PD-1 pathway in NSCLC patients.
Highlights
Lung cancer remains the leading cause of cancerrelated death in the United States, with approximately 160,000 deaths every year
We report that surface expression of programmed cell death-1 (PD-1) on CD4+ T cells has a prognostic value in non-small cell lung cancer (NSCLC) patients, as high expression of PD-1 is associated with a shorter progression-free survival and overall survival
Expression of PD-1 on CD8+ T cells was comparable between NSCLC patients and healthy donors (HD)
Summary
Lung cancer remains the leading cause of cancerrelated death in the United States, with approximately 160,000 deaths every year. The majority of these patients have non-small cell lung cancer (NSCLC). The prognosis for metastatic NSCLC is generally poor with the overall five-year survival of < 5% [1]. Platinumbased chemotherapy has been the standard treatment for advanced NSCLC in addition to targeting patientspecific tumor driving mutations (i.e. EGFR) [2, 3]. These therapies, are limited by significant toxicities and development of resistance. Only a fraction of these patients have targetable mutations in their tumor
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