A Subset of PD-1-Expressing CD56(bright) NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer

SIMPLE SUMMARY: In recent years, studies in cancer immunotherapy have focused on finding predictive response biomarkers to anticipate which patients will respond to each kind of treatment, optimizing treatment strategy and reducing toxicities and costs. Unfortunately, these studies are still limited, and no conclusive results have been obtained. This study was designed to prospectively analyze a cohort of lung cancer patients receiving immunotherapy attempting to determine cellular biomarkers of response, as T-lymphocyte and natural killer (NK) cell subsets, in peripheral blood. Despite previous studies, none of these populations have been identified yet with clinical relevance to be established in clinical practice. In our study, we have identified a subset of circulating CD56+CD16-PD-1+ NK cells showing a good predictive ability. These results contribute to the development of precision medicine protocols where we could stratify patients according to the expected treatment response to choose the best option for each patient. ABSTRACT: (1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3−CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3−CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56(bright) NK cell subpopulation (CD56+CD3−CD16−PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.