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Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities

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 dispari...

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Autores principales: Curran, Thomas, Sun, Zequn, Gerry, Brielle, Findlay, Victoria J., Wallace, Kristin, Li, Zihai, Paulos, Chrystal, Ford, Marvella, Rubinstein, Mark P., Chung, Dongjun, Camp, E. Ramsay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940243/
https://www.ncbi.nlm.nih.gov/pubmed/33560598
http://dx.doi.org/10.1002/cam4.3753
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author Curran, Thomas
Sun, Zequn
Gerry, Brielle
Findlay, Victoria J.
Wallace, Kristin
Li, Zihai
Paulos, Chrystal
Ford, Marvella
Rubinstein, Mark P.
Chung, Dongjun
Camp, E. Ramsay
author_facet Curran, Thomas
Sun, Zequn
Gerry, Brielle
Findlay, Victoria J.
Wallace, Kristin
Li, Zihai
Paulos, Chrystal
Ford, Marvella
Rubinstein, Mark P.
Chung, Dongjun
Camp, E. Ramsay
author_sort Curran, Thomas
collection PubMed
description 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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spelling pubmed-79402432021-03-16 Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities Curran, Thomas Sun, Zequn Gerry, Brielle Findlay, Victoria J. Wallace, Kristin Li, Zihai Paulos, Chrystal Ford, Marvella Rubinstein, Mark P. Chung, Dongjun Camp, E. Ramsay Cancer Med Cancer Biology 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. John Wiley and Sons Inc. 2021-02-09 /pmc/articles/PMC7940243/ /pubmed/33560598 http://dx.doi.org/10.1002/cam4.3753 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Curran, Thomas
Sun, Zequn
Gerry, Brielle
Findlay, Victoria J.
Wallace, Kristin
Li, Zihai
Paulos, Chrystal
Ford, Marvella
Rubinstein, Mark P.
Chung, Dongjun
Camp, E. Ramsay
Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title_full Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title_fullStr Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title_full_unstemmed Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title_short Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
title_sort differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940243/
https://www.ncbi.nlm.nih.gov/pubmed/33560598
http://dx.doi.org/10.1002/cam4.3753
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