Thomas Curran1,2, Zequn Sun3, Brielle Gerry1, Victoria J Findlay4, Kristin Wallace3, Zihai Li5,6, Chrystal Paulos5,7, Marvella Ford3, Mark P Rubinstein4,5, Dongjun Chung6,8, E Ramsay Camp9,10. 1. Department of Surgery, Medical University of South Carolina, Charleston, SC, USA. 2. Ralph H. Johnson VA Medical Center, Charleston, SC, USA. 3. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. 4. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA. 5. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA. 6. The Pelotonia Institute for Immuno-Oncology, Ohio State University Comprehensive Cancer Center - James, Columbus, OH, USA. 7. Department of Surgery/Department of Microbiology and Immunology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA. 8. Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. 9. Department of Surgery, Baylor College of Medicine, Houston, TX, USA. 10. Michael E. DeBakey VA Medical Center, Houston, TX, USA.
Abstract
BACKGROUND: Disparities in colon cancer (CC) outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying CC disparities, we compared the immunogenomic signatures of CC from African American and European American patients. METHODS: We identified all CC patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed. RESULTS: Of the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p = 0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age, and disease stage. Immunostimulatory and immunoinhibitory gene profiles including major histocompatibility complex expression differed by race. CONCLUSIONS: Differences in the tumor immune microenvironment of African American as compared to European American CC specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.
BACKGROUND: Disparities in colon cancer (CC) outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying CC disparities, we compared the immunogenomic signatures of CC from African American and European American patients. METHODS: We identified all CC patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed. RESULTS: Of the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p = 0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age, and disease stage. Immunostimulatory and immunoinhibitory gene profiles including major histocompatibility complex expression differed by race. CONCLUSIONS: Differences in the tumor immune microenvironment of African American as compared to European American CC specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.
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