Tumor Infiltrating Cytotoxic CD8 T‑Cells Predict Clinical Outcome of Neuroblastoma in Children

Abstract

Abstract Context: Neuroblastoma is often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against cancer. CD8+ lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8+ cytotoxic lymphocytes in Neuroblastoma. Subjects and Methods:Tumor-infiltrating CD8+ lymphocytes were assessed by immunohistochemical staining of tumor tissue from 36 neuroblastoma from April 2008 to May 2015. The number of CD8+ T-cells was counted in tumor nest (intratumoral) and in the fibrovascular stroma of tumor (peritumoral), and their relationship with clinicopathologic outcome was determined. Results: The total number of CD8+ cells was inversely correlated with tumor histology grade (P < 0.001), vascular invasion (P < 0.001), capsular invasion (P < 0.002), calcification (P < 0.005), necrosis of tumor (P < 0.001), regional lymph nodes invasion (P < 0.003), distant metastasis (P < 0.003), stage (P < 0.003), and was positive correlated with N-myc oncogene presentation (P < 0.002) in neuroblastoma. However, there were no correlation between patient's age, sex, and size of tumor with infiltration of CD8+ cells (P < 0.097, P < 0.142, and P < 0.722, respectively). Conclusions: In this analysis, total CD8 T-cell count was a dependent prognostic factor in children. Total number and stromal CD8 lymphocytes were associated with better patient survival (P < 0.003 and P < 0.05, respectively) in children. These results suggest that tumor-infiltrating CD8 T lymphocytes have antitumor activity and influence the behavior of neuroblastoma and might be potentially be exploited in the treatment of neuroblastoma in children.