Manjunath Y, et al. J Thorac Oncol 2020.
INTRODUCTION: Various subtypes of circulating cancer-associated cells in the blood are described. A unique circulating, large and polymorphonuclear cell with a dual epithelial and myeloid phenotype has been suggested to be a tumor-macrophage fusion cell (TMF). The goal of the study was to identify the impact of distinct TMFs on survival in non-small cell lung cancer (NSCLC) patients.
METHODS: In a prospective trial, 7.5 ml of whole blood was collected. Following microfilter enrichment immunofluorescent staining was performed, identifying TMFs as ≥30 μm sized and dual epithelial (cytokeratin (CK) 8/18/19/EpCAM+) and myeloid/macrophage positive (CD14/45+) cells with ≥1 DAPI+ nucleus.
RESULTS: Circulating TMFs were identified in 88/115 (76.5%) of NSCLC patients (mean 3.052 (SEM ±0.306); median 2 (range 0-17)), but were rare in long-term smokers without cancer (6/87 (6.9%); 0.081 (±0.034); 0 (0-2)), and absent in 20 healthy controls. Comparing presence of TMFs in NSCLC patients versus smokers without cancer, specificity was 93.1% (95% confidence interval (CI): 85.6-97.4%) and sensitivity 76.5% (95% CI: 67.7%-83.9%). TMF counts correlated with AJCC tumor stages. Importantly, >1 TMF and giant TMFs sized ≥50 μm were associated with significantly shorter overall and cancer-specific disease-free survival after curative surgery for stage I-IIIA. Giant TMFs ≥50 μm size were an independent survival predictor by multivariate analysis.
CONCLUSIONS: Circulating, in particular giant TMFs are associated with an aggressive clinical behavior in surgically treated NSCLC patients. The biological role of unique TMFs will need to be further investigated, as these may have a potential impact on immune responses towards the cancer.