An important mechanism by which pancreatic cancer avoids anti-tumor immunity is by recruiting regulatory T cells (Treg) to the tumor microenvironment. Recent studies suggest that suppressor Treg and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Since IL-6 in the presence of TGF-β has been shown to inhibit Treg development and induce Th17 cells, we hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression. Pan02 murine pancreatic tumor cells that secrete TGF-β were transduced with the gene encoding IL-6. C57BL/6 mice were injected subcutaneously with wildtype (WT Pan02), empty vector (EV Pan02), or IL-6 transduced Pan02 cells (IL-6 Pan02) to investigate the impact of IL-6 secretion in the tumor microenvironment. Mice bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and better overall median survival compared with mice bearing WT or EV Pan02 tumors. Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4+IL-23R+ cells and CD4+IL-17+ cells) in tumors of the IL-6 Pan02 group compared with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4+ tumor-infiltrating lymphocytes was substantiated at the cellular level by flow cytometry and ELISPOT assay, and mRNA level for RORγt and IL-23 receptor by RT-PCR. Thus, the addition of IL-6 to the tumor microenvironment skews the balance toward Th17 cells in a murine model of pancreatic cancer. The delayed tumor growth and improved survival suggests that induction of Th17 in the tumor microenvironment produces an anti-tumor effect.
Male breast cancer (MBC) accounts for approximately 1% of all breast cancers,
limiting the data characterizing clinicopathologic features and treatment
outcomes in patients with MBC. This paucity of data has led to most of our
treatment guidance being extrapolated from patients with female breast cancer
(FBC). From 1998 to 2012, data were captured using the National Cancer Database
to identify patients with nonmetastatic MBC (n = 23 305) and FBC (n = 2 678
061). Tumor and clinicopathologic features were obtained and compared. Patients
with MBC were more likely to have invasive disease, T2-4 tumors, centrally
located tumors, positive lymph nodes, estrogen receptor–positive or progesterone
receptor–positive tumors, lymphovascular space invasion, and were less likely to
have Her2/neu-positive or triple-negative tumors. All of these differences were
statistically significant (P < .001). Treatment comparisons
showed that patients with MBC were more likely to undergo mastectomy and less
likely to undergo breast-conserving surgery with postoperative radiation
utilization found to be less in patients with MBC, both as part of
breast-conserving therapy (BCT) and for postmastectomy radiation treatment
(PMRT) (P < .001). Stage-by-stage comparisons showed that
median survival, 5-year, and 10-year overall survival (OS) rates are lower in
patients with MBC vs patients with FBC (P < .001). The
utilization of adjuvant radiation, both BCT and PMRT, was shown to improve 5-
and 10-year OS (P < .001). Male breast cancer
clinicopathologic features appear to be unfavorable in relation to FBC and
adjuvant radiation is shown beneficial in survival outcomes. Further
investigation is needed to help guide future utilization and treatment with
radiation, systemic, and endocrine manipulation in this small population of
patients with MBC.
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