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An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential...

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Autores principales: Geddes, Andrea E., Ray, Anita L., Nofchissey, Robert A., Esmaeili, Azadeh, Saunders, Apryl, Bender, Dawn E., Khan, Maaz, Aravindan, Sheeja, Ahrendsen, Jared T., Li, Min, Fung, Kar-Ming, Jayaraman, Muralidharan, Yang, Jingxuan, Booth, Kristina K., Dunn, Gary D., Carter, Steven N., Morris, Katherine T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651089/
https://www.ncbi.nlm.nih.gov/pubmed/36387163
http://dx.doi.org/10.3389/fonc.2022.986103
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author Geddes, Andrea E.
Ray, Anita L.
Nofchissey, Robert A.
Esmaeili, Azadeh
Saunders, Apryl
Bender, Dawn E.
Khan, Maaz
Aravindan, Sheeja
Ahrendsen, Jared T.
Li, Min
Fung, Kar-Ming
Jayaraman, Muralidharan
Yang, Jingxuan
Booth, Kristina K.
Dunn, Gary D.
Carter, Steven N.
Morris, Katherine T.
author_facet Geddes, Andrea E.
Ray, Anita L.
Nofchissey, Robert A.
Esmaeili, Azadeh
Saunders, Apryl
Bender, Dawn E.
Khan, Maaz
Aravindan, Sheeja
Ahrendsen, Jared T.
Li, Min
Fung, Kar-Ming
Jayaraman, Muralidharan
Yang, Jingxuan
Booth, Kristina K.
Dunn, Gary D.
Carter, Steven N.
Morris, Katherine T.
author_sort Geddes, Andrea E.
collection PubMed
description Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.
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spelling pubmed-96510892022-11-15 An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer Geddes, Andrea E. Ray, Anita L. Nofchissey, Robert A. Esmaeili, Azadeh Saunders, Apryl Bender, Dawn E. Khan, Maaz Aravindan, Sheeja Ahrendsen, Jared T. Li, Min Fung, Kar-Ming Jayaraman, Muralidharan Yang, Jingxuan Booth, Kristina K. Dunn, Gary D. Carter, Steven N. Morris, Katherine T. Front Oncol Oncology Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC. Frontiers Media S.A. 2022-10-28 /pmc/articles/PMC9651089/ /pubmed/36387163 http://dx.doi.org/10.3389/fonc.2022.986103 Text en Copyright © 2022 Geddes, Ray, Nofchissey, Esmaeili, Saunders, Bender, Khan, Aravindan, Ahrendsen, Li, Fung, Jayaraman, Yang, Booth, Dunn, Carter and Morris https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Geddes, Andrea E.
Ray, Anita L.
Nofchissey, Robert A.
Esmaeili, Azadeh
Saunders, Apryl
Bender, Dawn E.
Khan, Maaz
Aravindan, Sheeja
Ahrendsen, Jared T.
Li, Min
Fung, Kar-Ming
Jayaraman, Muralidharan
Yang, Jingxuan
Booth, Kristina K.
Dunn, Gary D.
Carter, Steven N.
Morris, Katherine T.
An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title_full An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title_fullStr An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title_full_unstemmed An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title_short An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
title_sort analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9651089/
https://www.ncbi.nlm.nih.gov/pubmed/36387163
http://dx.doi.org/10.3389/fonc.2022.986103
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