Abstract
BackgroundAfrican Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease.MethodsWe selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch.ResultsWe observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001).ConclusionsOverall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive (‘cold’) tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.
Highlights
Colorectal cancer (CRC) is the third most common malignancy among men and women in the US and the second leading cause of cancer death [1]
AAs had a higher prevalence of proximal adenomas (66% vs. 40%) than Caucasian Americans (CAs) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04)
AAs compared to CAs presented with a similar prevalence of high-grade dysplasia lesions compared to CAs (53% vs. 40%, p=0.18)
Summary
Colorectal cancer (CRC) is the third most common malignancy among men and women in the US and the second leading cause of cancer death [1]. African Americans (AAs) experience higher incidence and mortality from CRC than Caucasian Americans (CAs), especially at younger ages [2,3,4,5]. Recent evidence has identified lower cytotoxic responses (e.g., Granzyme B, IFNG) in CRCs of AAs compared to CAs [16,17,18,19], yet higher expression for inflammatory or markers of exhausted T-cells [19]. Understanding whether racial differences in immune signatures are evident in earlier phases of carcinogenesis have important consequences for primary and secondary prevention [20, 21]. African Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease
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