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Supplemental Digital Content is available in the text Objective: To determine if intraoperative near-infrared (NIR) imaging carries benefit in resection of pancreatic neoplasms. Background: Resection of pancreatic malignancies is hindered by high rates of local and distant recurrence from positive margins and unrecognized metastases. Improved tumor visualization could improve outcomes. We hypothesized that intraoperative NIR imaging with a clinically approved optical contrast agent could serve as a useful adjunct in assessing margins and extent of disease during pancreatic resections. Methods: Twenty patients were enrolled in an open-label clinical trial from July 2016 to May 2018. Subjects received second window indocyanine green (ICG) (2.5–5 mg/kg) 24 hours prior to pancreatic resection. NIR imaging was performed during staging laparoscopy and after pancreas mobilization in situ and following resection ex vivo. Tumor fluorescence was quantified using tumor-to-background ratio (TBR). Fluorescence at the specimen margin was compared to pathology evaluation. Results: Procedures included 9 pancreaticoduodenectomies, 10 distal pancreatectomies, and 1 total pancreatectomy; 21 total specimens were obtained. Three out of 8 noninvasive tumors were fluorescent (mean TBR 2.59 ± 2.57). Twelve out of 13 invasive malignancies (n = 12 pancreatic adenocarcinoma, n = 1 cholangiocarcinoma) were fluorescent (mean TBR 4.42 ± 2.91). Fluorescence at the transection margin correlated with final pathologic assessment in 12 of 13 patients. Following neoadjuvant therapy, 4 of 5 tumors were fluorescent; these 4 tumors showed no treatment response on pathology assessment. One tumor had a significant treatment response and showed no fluorescence. Conclusions: Second window ICG reliably accumulates in invasive pancreatic malignancies and provides real-time feedback during pancreatectomy. NIR imaging may help to assess the response to neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Despite the success of vaccines against some microbial pathogens, their utility in the prevention and treatment of cancer has thus far been limited. We have previously demonstrated that vaccination with dendritic cells activated with the TLR-4 ligand LPS and IFN-γ promotes an antigen-specific anti-tumor response that prevents tumor recurrence. To evaluate this mechanistically, we here studied the effects of this TLR-activated DC on regulatory T cell activity. Dendritic cells activated with LPS and IFN- γ negated the effects of regulatory T cells on responder cell proliferation. Restoration of responder cell proliferation was noted when TLR-activated dendritic cells were separated from both regulators and responders by a semi-permeable membrane. The effect is therefore mediated by a soluble factor but was independent of both IL-6 and IL-12. Furthermore, the soluble mediator appeared to act at least in part on the regulators themselves rather than responder cells exclusively. Because recent studies have demonstrated conversion of T regulatory cells into IL-17-producing effectors, we further questioned whether the TLR-activated dendritic cell would induce cytokine production and effector function in our system. We found that regulators produced a substantial amount of IFN- γ in the presence of TLR-activated dendritic cells but not immature dendritic cells. IFN-γ production was associated with upregulation of the Th1 transcriptional regulator T-bet, and a significant fraction of IFN-γ-producing regulators coexpressed T-bet and FoxP3. While the effects of the LPS-activated dendritic cell on responder cell proliferation were IL-12 independent, upregulation of T-bet was inhibited by a neutralizing anti-IL-12 antibody. Collectively, these and prior data suggest that varying innate immune signals may direct the phenotype of the immune response in part by inhibiting suppressor T cells and promoting differentiation of these regulators into particular subsets of effectors. [ABSTRACT FROM AUTHOR]