Immune profiles of colorectal cancer in African American and Caucasian individuals

Publication Date

July 2019

Location

LSU Health Medical Education Building

Document Type

Abstract

Start Date

26-7-2019 9:00 AM

End Date

26-7-2019 12:00 PM

Description

Colorectal cancer (CRC) is one of the leading causes of cancer related deaths worldwide for both genders, but the prevalence of the disease in the U.S. is disproportionately higher in African American (AA) than in Caucasian (CA) individuals. Inflammation is considered a hallmark of cancer. The activity of inflammatory cells may lead not only to genetic instability but also to mechanisms such as tissue remodeling, angiogenesis, and treatment resistance. Recent data suggest a differential role played by immune cells in the development of CRC. Understanding how these cells are differentially associated with immune surveillance and how they can be modified to enhance future therapies, i.e. immunotherapy, is essential to reduce CRC disparities. This is particularly important in the context of the genetic differences that underlie higher inflammatory responses in some individuals. These responses may lead to changes in tumor cell transcriptome to adapt to the challenge of the host’s immune system. We have previously shown, in a highly admixed population, that European genetic ancestry is associated with adenomatous polyps (AP) and that African genetic ancestry is associated with CRC, even after adjusting for many non-genetic risk factors. We have recently shown that a correlation of the African ancestry and the presence of a pro-inflammatory haplotype in the ILB gene, -3737C/-1464G/-511T/-31C, increases the risk of CRC. Interestingly, our replication of the study in AA individuals with CRC showed an increased prevalence of the same haplotype. This haplotype has been associated with increased levels of transcription of the IL1B gene promoter. In addition, suppression of IL1-β responses decreases CRC burden in mouse models. This action seems to be carried out through changes in the type of cellular infiltration into the tumors. Taken together, these results suggest a significant role of the immune system in mediating the disparities of CRC observed the U.S. between AA and CA. Our long-term objective is to establish a correlation between the genomics of CRC with the immune response and cellular infiltration in African American individuals. The immediate goal of this study is to validate by real-time PCR recent findings in the lab showing a differential immune infiltration of CRC tissues from AA and CA. Similarly, our goal is to set up the conditions for the immunohistochemistry validation of these biomarkers as well as to determine the effect that secreted products from CRC cell lines may have on the expression of those markers in peripheral blood mononuclear cells (PBMC). We hypothesize that the degree and type of immune infiltration in colorectal cancer (CRC) tissues of AA individuals is different from those of CA.

Comments

Mentor: Jovanny Zabaleta Department of Pediatrics-Stanley S. Cancer Center

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Jul 26th, 9:00 AM Jul 26th, 12:00 PM

Immune profiles of colorectal cancer in African American and Caucasian individuals

LSU Health Medical Education Building

Colorectal cancer (CRC) is one of the leading causes of cancer related deaths worldwide for both genders, but the prevalence of the disease in the U.S. is disproportionately higher in African American (AA) than in Caucasian (CA) individuals. Inflammation is considered a hallmark of cancer. The activity of inflammatory cells may lead not only to genetic instability but also to mechanisms such as tissue remodeling, angiogenesis, and treatment resistance. Recent data suggest a differential role played by immune cells in the development of CRC. Understanding how these cells are differentially associated with immune surveillance and how they can be modified to enhance future therapies, i.e. immunotherapy, is essential to reduce CRC disparities. This is particularly important in the context of the genetic differences that underlie higher inflammatory responses in some individuals. These responses may lead to changes in tumor cell transcriptome to adapt to the challenge of the host’s immune system. We have previously shown, in a highly admixed population, that European genetic ancestry is associated with adenomatous polyps (AP) and that African genetic ancestry is associated with CRC, even after adjusting for many non-genetic risk factors. We have recently shown that a correlation of the African ancestry and the presence of a pro-inflammatory haplotype in the ILB gene, -3737C/-1464G/-511T/-31C, increases the risk of CRC. Interestingly, our replication of the study in AA individuals with CRC showed an increased prevalence of the same haplotype. This haplotype has been associated with increased levels of transcription of the IL1B gene promoter. In addition, suppression of IL1-β responses decreases CRC burden in mouse models. This action seems to be carried out through changes in the type of cellular infiltration into the tumors. Taken together, these results suggest a significant role of the immune system in mediating the disparities of CRC observed the U.S. between AA and CA. Our long-term objective is to establish a correlation between the genomics of CRC with the immune response and cellular infiltration in African American individuals. The immediate goal of this study is to validate by real-time PCR recent findings in the lab showing a differential immune infiltration of CRC tissues from AA and CA. Similarly, our goal is to set up the conditions for the immunohistochemistry validation of these biomarkers as well as to determine the effect that secreted products from CRC cell lines may have on the expression of those markers in peripheral blood mononuclear cells (PBMC). We hypothesize that the degree and type of immune infiltration in colorectal cancer (CRC) tissues of AA individuals is different from those of CA.