Abstract
BackgroundThe presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A+CD27−IgD−. These CD27−IgD− (double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue.MethodsA total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A+ B cells subsets were classified as either naïve (CD27−IgD+), affinity-matured (CD27+IgD−), early memory/germinal center cells (CD27+IgD+) or double-negative B cells (CD27−IgD−). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student’s t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman’s rank correlation.ResultsWe observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman’s coefficient of − 0.76.ConclusionsThis study is the first to observe the presence of CD27−IgD− double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.
Highlights
The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear
The double‐negative (CD79A+CD27−IgD−) B cell population is expanded in NSCLC tumors Previously it has been reported that the expression of B cell-related genes (2) and the presence of tumor infiltrating B cells (TIL-Bs) (4) correlate with early stage lung cancer survival
We characterized TIL-Bs in untreated NSCLC tumors and matched normal lung tissue to identify B cell subsets which might participate in anti-tumor immunity
Summary
The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. The tumor microenvironment is a complex dynamic network of stromal components, fibroblasts, endothelial cells, stem cells, and infiltrating immune cells, all Centuori et al J Transl Med (2018) 16:30 upregulation of B cell related genes [3], CD20+ B cell infiltration [4], and the presence of B cell-related tertiary lymphoid structures [5] to correlate with patient survival, suggesting that B cells may have influential roles in lung tumor immunity This supposition is challenged by data suggesting that humoral immune responses may instead attenuate T cell mediated tumor immunity [6]. It has been demonstrated that these cells can be detected in heathy individuals at low levels within peripheral blood and tonsils [7, 9], but are expanded in peripheral blood of elderly patients [10], patients with Alzheimer’s disease [11], rheumatoid arthritis [12], systemic lupus erythematosus [7], HIV [13], and rotavirus [8]
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