P2.04-06 Increased Plasma Cell % and Decreased B-Cells in Tumor Immune Infiltrates Are Associated with Worse Prognosis in Lung Adenocarcinomas

Abstract

Clinical significance of tumor-infiltrating plasma cells and B-cells in lung adenocarcinoma is not well known. CD3, CD20 and MUM1 immunostains were performed on representative tumor blocks selected from 120 consecutive lung adenocarcinoma cases resected. CD3-positive T-cells, CD20-positive B-cells, and MUM1-positive plasma cells were separately enumerated in the intraepithelial (IE) compartment and the stroma (ST) by digital image analyses. Distribution of measured tumor-infiltrating cells was systematically evaluated and their associations with patient’s overall survival (OS) modeled using Cox proportional hazards analysis. Median age of patients was 69 years (range, 46-91 years) and 52 patients were male. Eighty-two, 17, and 21 patients were tumor stage I, II, and III/IV, respectively. Ninety patients had surgery only; 30 had surgery with adjuvant chemotherapy and/or radiation therapy. Median numbers (interquartile range) of CD20-positive B-cells per 1mm2 in the tumor area (IE plus ST) and in IE compartment were 590 (224-1276) and 101 (38-109), respectively; the corresponding numbers of MUM1-positive plasma cells were 298 (180-605), and 67 (22-145), respectively. The percent of MUM1-positive plasma cells among all tumor immune infiltrate (i.e. MUM1-positive cells/[CD3-positive cells + CD20-positive cells + MUM1- positive cells] x 100) ranged from 0 to 60% (median 10%) in the tumor area and showed a significant association with OS by univariate Cox analysis (continuous variable; negative correlation with HR=12.50 [95% confidence interval [CI], 1.75-89.27]). There was a significant association between IE CD20-positive B-cells and the patient’s OS in univariate analysis (continuous variable; positive correlation with hazard ratio [HR]=0.81 (95% CI, 0.68-0.96). Both parameters remained significant by multivariate analysis. Cut-off points (low vs high) showing significant associations with patient’s OS were found by log-rank test (Table 1). High plasma cell % among immune infiltrate in the tumor area and low IE B-cell count were associated with worse prognosis in lung adenocarcinoma patients.