Plasmacytoid Dendritic Cell, Slan(+)-Monocyte and Natural Killer Cell Counts Function as Blood Cell-Based Biomarkers for Predicting Responses to Immune Checkpoint Inhibitor Monotherapy in Non-Small Cell Lung Cancer Patients

SIMPLE SUMMARY: The advent of therapy with immune checkpoint inhibitors (ICIs) has determined a significant survival benefit in patients with non-small cell lung cancer (NSCLC). However, 50–80% of patients do not respond to ICI monotherapy. Therefore, the identification of biomarkers for predicting NSCLC patient response to ICI monotherapy may help to select those who most likely obtain clinical/radiological benefits, in turn reducing the economic impact of health costs. In this study, we identified plasmacytoid dendritic cell, slan(+)-monocyte and natural killer cell counts as encouraging predictive biomarkers for ICI monotherapy in NSCLC patients. ABSTRACT: The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan(+)-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients.