Blood Immune Cell Biomarkers in Lung Cancer Patients Undergoing Treatment with a Combination of Chemotherapy and Immune Checkpoint Blockade.

Abstract

Simple SummaryTumor cells can evade destruction via immune cells by expressing coinhibitory membrane molecules, which can suppress tumor-specific T cells. Immune checkpoint inhibitor therapies act by blocking these inhibitory pathways via monoclonal antibodies. Although this type of immunotherapy has shown promising results for advanced cancers of different entities during recent years, an important challenge is to identify the baseline characteristics of patients who will mostly benefit from such treatment. Blood biomarkers have limitations to reflect the tumor microenvironment but are easier to handle than markers in tumor lesions. The aim of our study was to identify blood cell parameters correlating with patients’ survival in 90 patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy combined with chemotherapy. We found that patients with a neutrophil-to-lymphocyte ratio ≥6.1, a percentage of HLA-DRlow monocytes ≥22%, a frequency of slan+ non-classical monocytes <0.25%, and/or of dendritic cells ≤0.14% of leukocytes had a poorer prognosis. Long-term survivors were patients without any of the risk factors investigated. Our results implicate that blood neutrophil counts, special types of monocytes, and the number of blood dendritic cells might be useful predictive biomarkers for cancer patients’ survival.Although immune checkpoint inhibitor (ICI) therapies have improved the treatment of patients with advanced non-small cell lung cancer (NSCLC), several patients do not achieve durable clinical responses. Biomarkers for the prediction of therapy responses are urgently needed. To identify blood cell parameters correlating with patients’ survival, immune cells from 90 patients with NSCLC undergoing a combination of ICI and chemotherapy were prospectively monitored. At the time point of the first and third antibody administration, complete leukocyte blood count, the percentage of HLA-DRlow monocytes, the percentage of 6-Sulfo LacNAc (slan)+CD16+ non-classical monocytes, and the number of circulating dendritic cell (DC) subtypes, as well as T-, B-, and NK cells were determined by multi-color flow cytometry in peripheral blood. The prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis, with progression-free survival (PFS) as the main criterion. A total of 67 patients (74.4%) showed a partial remission or a stable disease, and 35% of patients even survived 12 months and longer. Patients with a neutrophil-to-lymphocyte ratio (NLR) ≥6.1, a frequency of HLA-DRlow monocytes ≥22%, of slan+ non-classical monocytes <0.25% of leukocytes, and/or a sum of myeloid DC (MDC) and plasmacytoid DC (PDC) ≤0.14% of leukocytes had a poorer prognosis. The hazard ratio for PFS was 2.097 (1.208–3.640) for the NLR, 1.964 (1.046–3.688) for HLA-DRlow monocytes, 3.202 (1.712–5.99) for slan+ non-classical monocytes, and 2.596 (1.478–4.56) for the MDC/PDC sum. Patients without any of the four risk factors showed the best PFS. Furthermore, low NK cell counts correlated with shorter PFS (cutoff 200 cells/µL). Female patients had lower baseline NK cell counts and a shorter PFS. Our study confirms the usefulness of blood immune cells as biomarkers for clinical response and survival in NSCLC patients undergoing a combined ICI/chemotherapy.