Blood Immune Cells as Biomarkers in Long-Term Surviving Patients with Advanced Non-Small-Cell Lung Cancer Undergoing a Combined Immune/Chemotherapy

SIMPLE SUMMARY: Tumor cells can evade recognition and killing via immune cells by expressing co-inhibitory membrane molecules, which suppress the activity of tumor-specific T cells. Immune checkpoint inhibitor (ICI) therapies act by blocking these inhibitory pathways via monoclonal antibodies. Due to the limited efficacy of ICI therapy, biomarkers have to be detected, a process that can identify patients who benefit from this long-term treatment. In this pilot study, immune monitoring of four blood cell markers was performed over time in advanced non-small cell lung cancer (NSCLC) patients undergoing combined immune/chemotherapy and surviving ≥12 months. We demonstrate that a low neutrophil/lymphocyte ratio (NLR), a low percentage of suppressive HLA-DR(low) monocytes, and/or clearly detectable numbers of slan+ non-classical monocytes and of dendritic cells can be predictive markers for therapy responses and treatment outcomes. These markers might have an impact on the treatment decisions for NSCLC patients, but need to be validated in larger cohorts. ABSTRACT: An important challenge remains in identifying the baseline characteristics of cancer patients who will mostly benefit from immune checkpoint inhibitor (ICI) therapies. Furthermore, biomarkers could help in the choice of an optimal therapy duration after a primary therapy response. In this pilot study, the time courses of four different immune cell parameters were followed in 12 patients with advanced non-small-cell lung cancer (NSCLC) undergoing ICI therapy combined with chemotherapy and surviving at least 12 months. Blood was collected at the time point of the first and third antibody administration, as well as after 12 months of patients’ survival. Using multi-color flow cytometry, two suppressive markers (neutrophil/lymphocyte ratio (NLR) and the frequency of circulating HLA-DR(low) monocytes), as well as two markers of an ongoing immune response (6-Sulfo LacNAc (slan)+ non-classical monocytes and dendritic cell (DC) subtypes), were determined. In most of those who survived > 12 months, a low NLR and a low number of HLA-DR(low) monocytes combined with clearly detectable numbers of slan+ non-classical monocytes and of DC subtypes were seen. Two of the patients had an increase in the suppressive markers paired with a decrease in slan+ non-classical monocytes and in DC subtypes, which, in at least one patient, was the correlate of an ongoing clinical progression. Our results implicate that the NLR, specific subtypes of monocytes, and the number of blood DCs might be useful predictive biomarkers for cancer patients during long-term treatment with ICI/chemotherapy.