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


CONCLUSIONS
The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value.
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. delitto@ufl.edu.
Daniel
D
Delitto
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. bsblack@ufl.edu.
Brian S
BS
Black
Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL, 32610, USA. HSorenson@dental.ufl.edu.
Heather L
HL
Sorenson
Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL, 32610, USA. aknowlton@dental.ufl.edu.
Andrea E
AE
Knowlton
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. Ryan.Thomas@surgery.ufl.edu.|North Florida/South Georgia Veterans Health System, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, 32610, USA. Ryan.Thomas@surgery.ufl.edu.
Ryan M
RM
Thomas
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. george.sarosi@surgery.ufl.edu.|North Florida/South Georgia Veterans Health System, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, 32610, USA. george.sarosi@surgery.ufl.edu.
George A
GA
Sarosi
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. lyle.moldawer@surgery.ufl.edu.
Lyle L
LL
Moldawer
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. kevin.behrns@surgery.ufl.edu.
Kevin E
KE
Behrns
Department of Pathology, College of Medicine, University of Florida Health Science Center, Gainesville, FL, 32610, USA. liu@pathology.ufl.edu.
Chen
C
Liu
Department of Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, FL, 32610, USA. thom.george@medicine.ufl.edu.
Thomas J
TJ
George
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. Jose.Trevino@surgery.ufl.edu.
Jose G
JG
Trevino
Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL, 32610, USA. swallet@dental.ufl.edu.
Shannon M
SM
Wallet
Department of Surgery, College of Medicine, University of Florida Health Science Center, Room 6116, Shands Hospital, 1600 SW Archer Rd, Gainesville, FL, 32610, USA. Steven.Hughes@surgery.ufl.edu.
Steven J
SJ
Hughes
D000230:Adenocarcinoma / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins