The tumor microenvironment, including its inflammatory components, regulates
tumor progression. Herein, we explore the relationship between
inflammation and the progression of
T-cell lymphoma in the cutaneous microenvironment. Injection of MBL2 murine T
lymphoma cells into ear skin of C57BL/6 and immunodeficient SCID/Beige mice resulted in
tumor formation in only the latter group. However, induction of skin
inflammation by one topical application of
DNFB following MBL2 inoculation in C57BL/6 mice resulted in progressive
high-grade lymphoma. The
DNFB-regulated
tumor formation was blocked by early, but not late, application of a potent topical
corticosteroid. At 2 days after implantation, a 10-fold decrease in MBL2 cell apoptosis was detected in
DNFB-treated ears compared with vehicle control. After
DNFB treatment, Gr-1(high) neutrophils and F4/80(+) macrophages constituted the majority of
tumor-infiltrating CD45(+) leukocytes. Depletion of macrophages by
clodronate-containing
liposomes blocked the
tumor-promoting effect of
DNFB. Transcriptional profiling of inflammatory
cytokines and
chemokines after
DNFB treatment revealed robust changes in genes that are important in chemotaxis, proliferation, and apoptosis. Activation of oncogenic signal pathways, including NF-κB, was also detected. This work provides insights into the cellular and molecular pathways that mediate
lymphoma progression and may have applicability to human
cutaneous T-cell lymphomas.