Tumor Microenvironment CD14(+) Cells Correlate with Poor Overall Survival in Patients with Early-Stage Lung Adenocarcinoma

SIMPLE SUMMARY: Lung cancer is the leading cause of cancer-related deaths worldwide in part due to high rates of recurrence even with early-stage disease. This suggests that new biomarkers are needed to improve predictions for patient outcomes and better understand the underlying biology that drives poor outcomes. We believe the immune cells within the tumor microenvironment (TME) are a key differentiator between patients who are cured and patients who experience lung cancer relapse. In this study, we investigated the presence of CD14(+) cells within the lung adenocarcinoma TME through immunohistochemistry and found that higher levels of CD14(+) cells were correlated with shorter patient survival. In vitro studies revealed a bi-directional cross-talk between CD14(+) cells and lung cancer that improved lung cancer cell recovery after chemotherapy. Our observations suggest that TME CD14(+) infiltration is a prognostic marker in lung cancer and that further studies are needed to understand CD14(+)-cell-mediated mechanisms that influence patient outcomes. ABSTRACT: Patients with early-stage lung adenocarcinoma have a high risk of recurrent or metastatic disease despite undergoing curative intent therapy. We hypothesized that increased CD14(+) cells within the tumor microenvironment (TME) could stratify patient outcomes. Immunohistochemistry for CD14 was performed on 189 specimens from patients with lung adenocarcinoma who underwent curative intent surgery. Outcomes and associations with clinical and pathologic variables were determined. In vitro studies utilized a coculture system to model the lung cancer TME containing CD14(+) cells. Patients with high levels of TME CD14(+) cells experienced a median overall survival of 5.5 years compared with 8.3 and 10.7 years for those with moderate or low CD14 levels, respectively (p < 0.001). Increased CD14(+) cell tumor infiltration was associated with a higher stage at diagnosis and more positive lymph nodes at the time of surgery. This prognostic capacity remained even for patients with early-stage disease. Using an in vitro model system, we found that CD14(+) cells reduced chemotherapy-induced cancer cell death. These data suggest that CD14(+) cells are a biomarker for poor prognosis in early-stage lung adenocarcinoma and may promote tumor survival. CD14(+) cell integration into the lung cancer TME can occur early in the disease and may be a promising new therapeutic avenue.