Increased Plasma Cells and Decreased B-cells in Tumor Infiltrating Lymphocytes are Associated with Worse Survival in Lung Adenocarcinomas

INTRODUCTION: Clinical significance of tumor-infiltrating plasma cells and B-cells in lung adenocarcinoma is not well known. METHODS: CD3, CD20 and MUM1 immunostains were performed on representative tumor blocks selected from 120 consecutive lung adenocarcinoma cases treated by surgical resection at Mayo Clinic Rochester. CD3(+) T-cells, CD20(+) B-cells, and MUM1(+) plasma cells were enumerated separately in the intraepithelial (IE) compartment and the stroma (ST) by digital image analyses using whole sections. Measured tumor-infiltrating plasma cells and B-cells were correlated with patient’s overall survival (OS) using Cox proportional hazards analysis. RESULTS: Median age of patients was 69 years (range, 46-91 years) and 52 were male. Median numbers (interquartile range) of CD20(+) B-cells per 1mm(2) of tumor area (IE plus ST) and IE compartment within tumor area were 590 (224-1276) and 101 (38-109), respectively; the corresponding numbers of MUM1(+) plasma cells were 298 (180-605), and 67 (22-145), respectively. The proportion of MUM1(+) plasma cell among all TILs (MUM1(+) cells/[CD3(+) cells +CD20(+) cells+MUM1(+) cells] × 100) ranged 1%-59% (median13%) in the tumor area and showed a significant association with OS by univariate Cox analysis (negative correlation with hazard ratio (HR)=12.50 [95% confidence interval (CI), 1.75-89.27]). There was a significant association between IE CD20(+) B-cells and the patient’s OS in univariate analysis (positive correlation with HR=0.81 [95% CI, 0.68-0.96]). Both parameters remained significant by multivariate analysis. CONCLUSION: High plasma cell % among TILs in the tumor area and low IE B-cell count were associated with worse prognosis in lung adenocarcinoma patients.