Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Oct 24:15:783.
doi: 10.1186/s12885-015-1820-x.

The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival

Daniel Delitto  1 , Brian S Black  2 , Heather L Sorenson  3 , Andrea E Knowlton  4 , Ryan M Thomas  5   6 , George A Sarosi  7   8 , Lyle L Moldawer  9 , Kevin E Behrns  10 , Chen Liu  11 , Thomas J George  12 , Jose G Trevino  13 , Shannon M Wallet  14 , Steven J Hughes  15
Affiliations

The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival

Daniel Delitto et al. BMC Cancer. .

Abstract

Background: The tumor microenvironment impacts pancreatic cancer (PC) development, progression and metastasis. How intratumoral inflammatory mediators modulate this biology remains poorly understood. We hypothesized that the inflammatory milieu within the PC microenvironment would correlate with clinicopathologic findings and survival.

Methods: Pancreatic specimens from normal pancreas (n = 6), chronic pancreatitis (n = 9) and pancreatic adenocarcinoma (n = 36) were homogenized immediately upon resection. Homogenates were subjected to multiplex analysis of 41 inflammatory mediators.

Results: Twenty-three mediators were significantly elevated in adenocarcinoma specimens compared to nonmalignant controls. Increased intratumoral IL-8 concentrations associated with larger tumors (P = .045) and poor differentiation (P = .038); the administration of neoadjuvant chemotherapy associated with reduced IL-8 concentrations (P = .003). Neoadjuvant therapy was also associated with elevated concentrations of Flt-3 L (P = .005). Elevated levels of pro-inflammatory cytokines IL-1β (P = .017) and TNFα (P = .033) were associated with a poor histopathologic response to neoadjuvant therapy. Elevated concentrations of G-CSF (P = .016) and PDGF-AA (P = .012) correlated with reduced overall survival. Conversely, elevated concentrations of FGF-2 (P = .038), TNFα (P = .031) and MIP-1α (P = .036) were associated with prolonged survival.

Conclusion: The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Th1-associated cytokines within the tumor microenvironment correlate with treatment resistance in PC. Distributions are displayed comparing intratumoral concentrations of a IL-1β and b TNFα in homogenates of pancreatic adenocarcinoma with histopathologic response to neoadjuvant chemotherapy. Bars represent mean values with standard error of the mean. *P < 0.05 for each association using the Mann Whitney U test
Fig. 2
Fig. 2
Inflammatory milieu within the tumor microenvironment correlates with tumor grade. Intratumoral concentrations of a GM-CSF, b IL-8 and c IL-15 demonstrated significant correlations with high tumor grade. *P < 0.05 for each association using the Mann Whitney U test
Fig. 3
Fig. 3
Elements of the inflammatory milieu within the tumor microenvironment have prognostic value. Kaplan-Meier curves are plotted for a FGF-2, b MDC, c Flt-3 L and d IL-4 based on cutoffs at median cytokine concentrations in 36 pancreatic adenocarcinoma specimens. The log-rank test was used to compare differences. Significance was considered for those in which P < 0.05
See this image and copyright information in PMC

References

    1. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–2413. - PubMed
    1. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825. doi: 10.1056/NEJMoa1011923. - DOI - PubMed
    1. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–1966. doi: 10.1200/JCO.2006.07.9525. - DOI - PubMed
    1. Wolf AM, Pucci MJ, Gabale SD, McIntyre CA, Irizarry AM, Kennedy EP, et al. Safety of perioperative aspirin therapy in pancreatic operations. Surgery. 2014;155(1):39–46. doi: 10.1016/j.surg.2013.05.031. - DOI - PubMed
    1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921. doi: 10.1158/0008-5472.CAN-14-0155. - DOI - PubMed

Publication types

MeSH terms

Substances