In recent years it has been increasingly appreciated that B cells constitute a significant part of the immune infiltrate of solid tumors (1). In their interesting paper, Zirakzadeh et al. demonstrate that solid tumors and metastatic lymph nodes are enriched for terminally differentiated B cells, i.e., memory B cells and plasmablasts (2). They furthermore provide evidence that these tumor-associated B cells presumably represent tumor Ag-specific B lymphocytes, which have undergone clonal expansion. Our analysis of patients with esophageal cancer confirms the finding of a plasmacytosis in the peripheral blood (Fig. 1A). The accumulation of plasma cells seems to be a general phenomenon in many tumor entities, and is associated with a better prognosis (3, 4). In addition, we found an increase in CD24highCD38high B cells (Fig. 1A), a subset with regulatory capacity (5). Interestingly, while both adenocarcinoma and squamous cell carcinoma of the esophagus had similar percentages of plasmablasts, adenocarcinomas had a higher proportion of CD24highCD38high B cells (Fig. 1B). Because they solely used the Freiburg classification, Zirakzadeh et al. omit regulatory B cell subsets from their analyses. However, recent publications, including our study of local B cell–depletion in mycosis fungoides, demonstrate that targeting of regulatory B cells seems to be a promising therapeutic concept and that balance between regulatory and terminally differentiated B cells might be of importance (6, 7). Therefore, a detailed understanding of the composition of the B cell infiltrate in tumors will be necessary for the application of B cell–targeted therapeutic interventions for the immunotherapy of malignant diseases.

FIGURE 1.

Analysis of B cells in the peripheral blood of patients with esophageal cancer (n = 22). (A) The percentage of plasmablasts and CD24high CD38high B cells is significantly increased in the peripheral blood. (B) The B cell infiltrate differed in the histologic subtypes. Adenocarcinomas (n = 16) of the esophagus had a comparable percentage of plasmablasts but a higher proportion of CD24high CD38high B cells than squamous cell carcinoma (n = 6) of the esophagus. Bars represent means ± SEM. *p < 0.05.

FIGURE 1.

Analysis of B cells in the peripheral blood of patients with esophageal cancer (n = 22). (A) The percentage of plasmablasts and CD24high CD38high B cells is significantly increased in the peripheral blood. (B) The B cell infiltrate differed in the histologic subtypes. Adenocarcinomas (n = 16) of the esophagus had a comparable percentage of plasmablasts but a higher proportion of CD24high CD38high B cells than squamous cell carcinoma (n = 6) of the esophagus. Bars represent means ± SEM. *p < 0.05.

Close modal
1
Nelson
B. H.
2010
.
CD20+ B cells: the other tumor-infiltrating lymphocytes
.
J. Immunol.
185
:
4977
4982
.
2
Zirakzadeh
A. A.
,
Marits
P.
,
Sherif
A.
,
Winqvist
O.
.
2013
.
Multiplex B cell characterization in blood, lymph nodes, and tumors from patients with malignancies
.
J. Immunol.
190
:
5847
5855
.
3
Carpenter
E. L.
,
Mick
R.
,
Rech
A. J.
,
Beatty
G. L.
,
Colligon
T. A.
,
Rosenfeld
M. R.
,
Kaplan
D. E.
,
Chang
K.-M.
,
Domchek
S. M.
,
Kanetsky
P. A.
, et al
.
2009
.
Collapse of the CD27+ B-cell compartment associated with systemic plasmacytosis in patients with advanced melanoma and other cancers
.
Clin. Cancer Res.
15
:
4277
4287
.
4
Schmidt
M.
,
Hellwig
B.
,
Hammad
S.
,
Othman
A.
,
Lohr
M.
,
Chen
Z.
,
Boehm
D.
,
Gebhard
S.
,
Petry
I.
,
Lebrecht
A.
, et al
.
2012
.
A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors
.
Clin. Cancer Res.
18
:
2695
2703
.
5
Blair
P. A.
,
Noreña
L. Y.
,
Flores-Borja
F.
,
Rawlings
D. J.
,
Isenberg
D. A.
,
Ehrenstein
M. R.
,
Mauri
C.
.
2010
.
CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients
.
Immunity
32
:
129
140
.
6
Theurich
S.
,
Schlaak
M.
,
Steguweit
H.
,
Heukamp
L.
,
Wennhold
K.
,
Kurschat
P.
,
Rabenhorst
A.
,
Hartmann
K.
,
Schloesser
H.
,
Shimabukuro-Vornhagen
A.
, et al
.
Targeting tumor infiltrating B cells in cutaneous T-cell lymphoma
.
J. Clin. Oncol.
In press
.
7
Wejksza
K.
,
Lee-Chang
C.
,
Bodogai
M.
,
Bonzo
J.
,
Gonzalez
F. J.
,
Lehrmann
E.
,
Becker
K.
,
Biragyn
A.
.
2013
.
Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator-activated receptor α
.
J. Immunol.
190
:
2575
2584
.