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

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.

An integrated proteomic classifier to distinguish benign from malignant pulmonary nodules

“…APOA4 was found over expressed in the serum and the respiratory epithelium of atypical adenomatous hyperplasia patients [15]. CD14 + cells play an important role in tumor microenvironment, and a recent study shows that levels of CD14 + cells negatively correlate with overall survival of lung cancer patients [16], and CD14 + macrophages may exert a broader function in other cancers as well. As an actin-binding protein, profilin (PFN1) has been reported to induce tumor metastasis in non-small cell lung cancer [17].…”

Spatial proteomic profiling of tumor and stromal compartments in non‐small‐cell lung cancer identifies signatures associated with overall survival

“…67 Schenk et al also showed early-stage adenocarcinoma patients with increased CD14 + cells experienced a lower median OS of 5.5 years compared to 10.7 years for those with moderate or low CD14 expression levels. 68 This negative effect is most likely caused by the role of myeloid-derived suppressor cells (MDSCs), in encouraging tumor spread and contributing to an immunosuppressive environment. 69,70 We also confirmed that increased stromal CD14 is strongly related to poor survival outcomes corroborating the results of previous studies.…”

A novel iTreg‐related signature for prognostic prediction in lung adenocarcinoma

“…One study revealed that the preoperative neutrophil‐lymphocyte ratio is an independent prognostic factor in patients with LUAD after complete resection and could be considered a prognostic marker for LUAD after complete resection 14 . CD14 + cells have been identified as a biomarker of poor prognosis in the early stage of LUAD and could promote the survival of LUAD patients 15 . Another study found that a higher numbers of CD8 + cells in tumor tissues is associated with better overall survival than a moderate or low number of CD8 + cells and is considered a protective factor in LUAD patients 16 .…”

“… 14 CD14 + cells have been identified as a biomarker of poor prognosis in the early stage of LUAD and could promote the survival of LUAD patients. 15 Another study found that a higher numbers of CD8 + cells in tumor tissues is associated with better overall survival than a moderate or low number of CD8 + cells and is considered a protective factor in LUAD patients. 16 Therefore, immune cells in LUAD have tremendous research value for investigating the prognosis of LUAD and formulating new therapeutic approaches.…”