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INFILTRATION OF MACROPHAGES AND MICROENVIRONMENT INFLAMMATORY PROTEINS IN PANCREATIC DUCTAL ADENOCARCINOMA
Jordan A. McKean
*1, Gerik W. Tushoski-Alemán
1, Grace R. Thompson
1, Kelly M. Herremans
1, Andrea Riner
2, Patrick Underwood
2, Song Han
1, Steven J. Hughes
11Surgery, University of Florida, Gainesville, FL; 2Ohio State University, Columbus, OH
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a complex and heterogenous tumor microenvironment with limited immune cell involvement. Macrophages have been shown to orchestrate the presence of several anti-tumor immune cells through inflammatory proteins. We aimed to describe the degree to which CD68+ macrophage infiltrations associated with microenvironment inflammatory proteins and prognosis.
Methods: We assembled a tissue microarray of 59 treatment-naïve pancreatic ductal adenocarcinoma and 30 non-PDAC pancreas controls. TMAs were stained through immunohistochemistry for CD68+ cells and percent positive area was quantified using QuPath software. Matching tumors were probed with a 41-plex inflammatory assay. Survival, comparisons, and associations between CD68+ infiltration/inflammatory proteins were evaluated by Kaplan-Meier method, Wilcoxon Rank Sum Test, and Spearman R correlation.
Results: We observed significant heterogeneity in the abundance of macrophages in PDAC (Range = 0.52% to 16.82%, Median = 3.31%). PDAC maintained higher infiltration of CD68+ macrophages compared to non-PDAC tissue (3.31% vs 0.275%, respectively; p=<0.0001. A moderate difference in survival was observed in CD68+ high tumors (Upper 50%; 497 days) and CD68+ low tumors (Lower 50%; 304 days); p-value = 0.123. Multivariate analysis of covariates (Age, Sex, Grade, T/N State) were not significantly associated with CD68+ infiltration. Of the 41 inflammatory proteins assessed, Fractalkine was significantly associated with increased CD68+ infiltration (r = 0.284; p = 0.039; 95% CI = 0.015 to 0.515). IL-17A (r= -0.265; p= 0.055; 95% CI = -0.499 to 0.006) and IL-5 (r= -0.279, p=0.066; 95% CI = -0.532 to 0.019) were also moderately associated with decreased CD68+ infiltration.
Conclusions: Treatment-naïve PDAC has heterogenous infiltration of CD68+ macrophages and several microenvironment inflammatory proteins may be indicative of increased macrophage-tumor penetration. Future studies will evaluate the impact of these proteins on intratumoral M1- and M2-macrophage phenotypes.
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