Immune Responses Vary in Preinvasive Colorectal Lesions by Tumor Location and Histology.

Immune responses vary in colorectal cancers, which strongly influence prognosis. However, little is known about the variance in immune response within preinvasive lesions. The study aims to investigate how the immune contexture differs by clinicopathologic features (location, histology, dysplasia) associated with progression and recurrence in early carcinogenesis. We performed a cross-sectional study using preinvasive lesions from the surgical pathology laboratory at the Medical University of South Carolina. We stained the tissues with immunofluorescence antibodies, then scanned and analyzed expression using automated image analysis software. We stained CD117 as a marker of mast cells, CD4/RORC to indicate Th17 cells, MICA/B as a marker of NK-cell ligands, and also used antibodies directed against cytokines IL6, IL17A, and IFNγ. We used negative binomial regression analysis to compare analyte density counts by location, histology, degree of dysplasia adjusted for age, sex, race, and batch. All immune markers studied (except IL17a) had significantly higher density counts in the proximal colon than distal colon and rectum. Increases in villous histology were associated with significant decreases in immune responses for IL6, IL17a, NK ligand, and mast cells. No differences were observed in lesions with low- and high-grade dysplasia, except in mast cells. The lesions of the proximal colon were rich in immune infiltrate, paralleling the responses observed in normal mucosa and invasive disease. The diminishing immune response with increasing villous histology suggests an immunologically suppressive tumor environment. Our findings highlight the heterogeneity of the immune responses in preinvasive lesions, which may have implications for prevention strategies. PREVENTION RELEVANCE: Our study is focused on immune infiltrate expression in preinvasive colorectal lesions; our results suggest important differences by clinicopathologic features that have implications for immune prevention research.

Behavioral Economic Purchase Tasks to Estimate Demand for Novel Nicotine/tobacco Products and Prospectively Predict Future Use: Evidence From The Netherlands.

INTRODUCTION: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs. METHODS: Daily smokers (≥16 years) from the Netherlands completed an online survey in April 2014 (N = 1215). Purchase tasks were completed for FMCs, ECs, and VLNCs. Participants indicated the number of cigarettes they would consume in 24 h, across a range of prices (0-30 euro). The relationship between consumption and price was quantified into four indices of demand (intensity, Pmax, breakpoint, and essential value). A follow-up survey in July 2015 measured FMC and EC use. RESULTS: At baseline, greater demand was observed for FMCs relative to ECs and VLNCs across all demand indices, with no difference between ECs and VLNCs. At follow-up, greater baseline FMC demand (intensity, essential value) was associated with lower quit rates and higher relapse. EC demand (Pmax, breakpoint, essential value) was positively associated with any EC use between survey waves, past 30 day EC use, and EC purchase between waves. CONCLUSIONS: Smokers valued FMCs more than ECs or VLNCs, and FMCs were less sensitive to price increases. Demand indices predicted use of commercially available products over a 15 month period. To serve as viable substitutes for FMCs, ECs and VLNCs will need to be priced lower than FMCs. IMPLICATIONS: Purchase tasks can be adapted for novel nicotine/tobacco products as a means to efficiently quantify demand and predict use. Among current daily smokers, the demand for ECs and VLNCs is lower than FMCs.