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


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 1mm2 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.

We also analyzed the TILs in different compartments by using original value or ln converted value for those with outliers, to ensure appropriate statistical analysis. We also tried to find if there is any dichotomous number showing the significance in the survival analysis. There were multiple valid dichotomous cut offs.

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