1. Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;
2. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science, Jinan, Shandong, China;
3. Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science, Jinan, China;
4. Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC.
Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples. The staining was analyzed and scored by the pathologist who was blinded to the clinical pathological data of the patients.
Results: High CD8+ T cell infiltration was correlated significantly with squamous cell carcinoma histology (p=0.008). High PD-L1 expression (≥10%) was associated with high tumor status (p=0.043). Pearson's correlation test showed that CD56+ cells were negatively correlated with CD133 expression (r=-0.361, p<0.001) and weakly correlated with negative OCT-4 expression (r=-0.180, p=0.018). There was a strong positive correlation between CD8 and HLA class I (r=0.573, p<0.001). In the survival analysis, high CD8+ T cell infiltration is an independent predictor of improved disease-free survival and overall survival. Patients with low CD133 expression and high CD56 expression had a longer overall survival than those with high CD133 expression and/or low CD56 expression (p=0.013).
Conclusion: There is a negative correlation between CD56+ cells and cancer stem cell markers. This correlation may confirm the possibility that natural killer cells can target CD133+ cancer stem cells/cancer initiating cells in non-small cell lung cancer.
Keywords: Non-small cell lung cancer, CD133, OCT-4, CD8+ T cells, NK cells