Diversity in the oesophageal phenotypic response to gastro-oesophageal reflux: immunological determinants
R C Fitzgerald, B A Onwuegbusi, M Bajaj-Elliott, I T Saeed, W R Burnham, M J G Farthing, R C Fitzgerald, B A Onwuegbusi, M Bajaj-Elliott, I T Saeed, W R Burnham, M J G Farthing
Abstract
Background and aims: Approximately 10% of adults experience gastro-oesophageal reflux symptoms with a variable oesophageal response. A total of 60% have no endoscopic abnormality, 30% have oesophagitis, and 10% have Barrett's oesophagus. We investigated whether the inflammatory cell infiltrate and cytokine profiles of these clinical phenotypes merely vary in severity or are fundamentally different.
Methods: Patients with reflux symptoms and a normal oesophagus (n=18), oesophagitis (n=26), and Barrett's oesophagus (n=22 newly diagnosed, n=28 surveillance) were recruited. Endoscopic and histopathological degrees of inflammation were scored. Cytokine expression was determined by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry.
Results: In oesophagitis, endoscopic and histopathological grades of inflammation correlated highly. mRNA expression of proinflammatory interleukin (IL)-1beta, IL-8, and interferon gamma (IFN-gamma) were increased 3-10-fold compared with non-inflamed squamous or Barrett's oesophageal samples. There was a modest increase in anti-inflammatory IL-10 but no increase in IL-4. In Barrett's oesophagus, 29/50 had no endoscopic evidence of inflammation and histopathological inflammation was mild in 17/50 and moderate in 24/50, independent of acid suppressants. Expression of IL-1beta, IL-8, and IFN-gamma was similar to non-inflamed squamous mucosa. IL-10 was increased 1.6-fold similar to oesophagitis. IL-4 was increased fourfold, with 100-fold increase in IL-4/T cell receptor expression, compared with squamous oesophagus or oesophagitis.
Conclusions: Barrett's oesophagus is characterised by a distinct Th-2 predominant cytokine profile compared with the proinflammatory nature of oesophagitis. The specific oesophageal immune responses may influence disease development and progression.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f1.jpg)
Figure 2
Number of molecules of mRNA…
Figure 2
Number of molecules of mRNA per μg total RNA for T cell receptor…
Figure 3
Representative gels for T cell…
Figure 3
Representative gels for T cell receptor (TCR) (A) and the three proinflammatory cytokines…
Figure 4
Levels of proinflammatory cytokine mRNA…
Figure 4
Levels of proinflammatory cytokine mRNA expression (T cell receptor (TCR), interleukin (IL)-1β, and…
Figure 5
Number of molecules of mRNA…
Figure 5
Number of molecules of mRNA per μg total RNA for interleukin (IL)-10 (A)…
Figure 6
Sample gels for interleukin (IL)-10…
Figure 6
Sample gels for interleukin (IL)-10 (A) and IL-4 (B). The amounts of synthetic…
Figure 7
Number of molecules of interferon…
Figure 7
Number of molecules of interferon γ (IFN-γ) and interleukin (IL)-4 as a ratio…
Figure 8
Representative examples of the cellular…
Figure 8
Representative examples of the cellular source of cytokine protein expression is shown by…
Figure 9
Representative immunohistochemical staining for interleukin…
Figure 9
Representative immunohistochemical staining for interleukin (IL)-4 and IL-10. (A) Negative control (original magnification…
- The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups.Shapiro M, Green C, Faybush EM, Esquivel RF, Fass R. Shapiro M, et al. Aliment Pharmacol Ther. 2006 Jan 15;23(2):321-9. doi: 10.1111/j.1365-2036.2006.02747.x. Aliment Pharmacol Ther. 2006. PMID: 16393313
- Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?Frazzoni M, Manno M, De Micheli E, Savarino V. Frazzoni M, et al. Dig Liver Dis. 2006 Sep;38(9):643-8. doi: 10.1016/j.dld.2006.02.020. Epub 2006 Apr 14. Dig Liver Dis. 2006. PMID: 16627016
- Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Parrilla P, et al. Gut. 1990 Sep;31(9):964-7. doi: 10.1136/gut.31.9.964. Gut. 1990. PMID: 2210462 Free PMC article.
- Dyspepsia and Gastro-oesophageal Reflux: A Systematic Review [Internet].Swedish Council on Health Technology Assessment. Swedish Council on Health Technology Assessment. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. PMID: 28876800 Free Books & Documents. Review.
- Review article: management of oesophageal adenocarcinoma -- control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus.Jankowski JA, Anderson M. Jankowski JA, et al. Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:71-80; discussion 95-6. doi: 10.1111/j.1365-2036.2004.02143.x. Aliment Pharmacol Ther. 2004. PMID: 15456468 Review.
- Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.Zhang T, Zhang B, Tian W, Wei Y, Wang F, Yin X, Wei X, Liu J, Tang X. Zhang T, et al. Front Med (Lausanne). 2022 Sep 29;9:994534. doi: 10.3389/fmed.2022.994534. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36250094 Free PMC article.
- Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data.Morozov S, Sentsova T. Morozov S, et al. World J Clin Cases. 2022 Sep 16;10(26):9254-9263. doi: 10.12998/wjcc.v10.i26.9254. World J Clin Cases. 2022. PMID: 36159432 Free PMC article.
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?Zhang ML, Ran LQ, Wu MJ, Jia QC, Qin ZM, Peng YG. Zhang ML, et al. World J Clin Cases. 2022 Aug 26;10(24):8436-8442. doi: 10.12998/wjcc.v10.i24.8436. World J Clin Cases. 2022. PMID: 36157831 Free PMC article. Review.
- Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach.Sundaram S, Kim EN, Jones GM, Sivagnanam S, Tripathi M, Miremadi A, Di Pietro M, Coussens LM, Fitzgerald RC, Chang YH, Zhuang L. Sundaram S, et al. Front Immunol. 2022 May 19;13:874255. doi: 10.3389/fimmu.2022.874255. eCollection 2022. Front Immunol. 2022. PMID: 35663986 Free PMC article.
- Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?Borgmann M, Quante M. Borgmann M, et al. Cancers (Basel). 2022 Apr 30;14(9):2246. doi: 10.3390/cancers14092246. Cancers (Basel). 2022. PMID: 35565378 Free PMC article. Review.
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Barrett Esophagus / immunology*
- Cytokines / metabolism*
- Esophagitis / immunology*
- Female
- Gastroesophageal Reflux / immunology*
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Phenotype
- Prospective Studies
- RNA, Messenger / metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Th2 Cells / immunology*
- Cytokines
- RNA, Messenger
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f2.jpg)
Figure 3
Representative gels for T cell…
Figure 3
Representative gels for T cell receptor (TCR) (A) and the three proinflammatory cytokines…
Figure 4
Levels of proinflammatory cytokine mRNA…
Figure 4
Levels of proinflammatory cytokine mRNA expression (T cell receptor (TCR), interleukin (IL)-1β, and…
Figure 5
Number of molecules of mRNA…
Figure 5
Number of molecules of mRNA per μg total RNA for interleukin (IL)-10 (A)…
Figure 6
Sample gels for interleukin (IL)-10…
Figure 6
Sample gels for interleukin (IL)-10 (A) and IL-4 (B). The amounts of synthetic…
Figure 7
Number of molecules of interferon…
Figure 7
Number of molecules of interferon γ (IFN-γ) and interleukin (IL)-4 as a ratio…
Figure 8
Representative examples of the cellular…
Figure 8
Representative examples of the cellular source of cytokine protein expression is shown by…
Figure 9
Representative immunohistochemical staining for interleukin…
Figure 9
Representative immunohistochemical staining for interleukin (IL)-4 and IL-10. (A) Negative control (original magnification…
- The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups.Shapiro M, Green C, Faybush EM, Esquivel RF, Fass R. Shapiro M, et al. Aliment Pharmacol Ther. 2006 Jan 15;23(2):321-9. doi: 10.1111/j.1365-2036.2006.02747.x. Aliment Pharmacol Ther. 2006. PMID: 16393313
- Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?Frazzoni M, Manno M, De Micheli E, Savarino V. Frazzoni M, et al. Dig Liver Dis. 2006 Sep;38(9):643-8. doi: 10.1016/j.dld.2006.02.020. Epub 2006 Apr 14. Dig Liver Dis. 2006. PMID: 16627016
- Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Parrilla P, et al. Gut. 1990 Sep;31(9):964-7. doi: 10.1136/gut.31.9.964. Gut. 1990. PMID: 2210462 Free PMC article.
- Dyspepsia and Gastro-oesophageal Reflux: A Systematic Review [Internet].Swedish Council on Health Technology Assessment. Swedish Council on Health Technology Assessment. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. PMID: 28876800 Free Books & Documents. Review.
- Review article: management of oesophageal adenocarcinoma -- control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus.Jankowski JA, Anderson M. Jankowski JA, et al. Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:71-80; discussion 95-6. doi: 10.1111/j.1365-2036.2004.02143.x. Aliment Pharmacol Ther. 2004. PMID: 15456468 Review.
- Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.Zhang T, Zhang B, Tian W, Wei Y, Wang F, Yin X, Wei X, Liu J, Tang X. Zhang T, et al. Front Med (Lausanne). 2022 Sep 29;9:994534. doi: 10.3389/fmed.2022.994534. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36250094 Free PMC article.
- Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data.Morozov S, Sentsova T. Morozov S, et al. World J Clin Cases. 2022 Sep 16;10(26):9254-9263. doi: 10.12998/wjcc.v10.i26.9254. World J Clin Cases. 2022. PMID: 36159432 Free PMC article.
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?Zhang ML, Ran LQ, Wu MJ, Jia QC, Qin ZM, Peng YG. Zhang ML, et al. World J Clin Cases. 2022 Aug 26;10(24):8436-8442. doi: 10.12998/wjcc.v10.i24.8436. World J Clin Cases. 2022. PMID: 36157831 Free PMC article. Review.
- Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach.Sundaram S, Kim EN, Jones GM, Sivagnanam S, Tripathi M, Miremadi A, Di Pietro M, Coussens LM, Fitzgerald RC, Chang YH, Zhuang L. Sundaram S, et al. Front Immunol. 2022 May 19;13:874255. doi: 10.3389/fimmu.2022.874255. eCollection 2022. Front Immunol. 2022. PMID: 35663986 Free PMC article.
- Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?Borgmann M, Quante M. Borgmann M, et al. Cancers (Basel). 2022 Apr 30;14(9):2246. doi: 10.3390/cancers14092246. Cancers (Basel). 2022. PMID: 35565378 Free PMC article. Review.
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Barrett Esophagus / immunology*
- Cytokines / metabolism*
- Esophagitis / immunology*
- Female
- Gastroesophageal Reflux / immunology*
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Phenotype
- Prospective Studies
- RNA, Messenger / metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Th2 Cells / immunology*
- Cytokines
- RNA, Messenger
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f3.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f4.jpg)
Figure 5
Number of molecules of mRNA…
Figure 5
Number of molecules of mRNA per μg total RNA for interleukin (IL)-10 (A)…
Figure 6
Sample gels for interleukin (IL)-10…
Figure 6
Sample gels for interleukin (IL)-10 (A) and IL-4 (B). The amounts of synthetic…
Figure 7
Number of molecules of interferon…
Figure 7
Number of molecules of interferon γ (IFN-γ) and interleukin (IL)-4 as a ratio…
Figure 8
Representative examples of the cellular…
Figure 8
Representative examples of the cellular source of cytokine protein expression is shown by…
Figure 9
Representative immunohistochemical staining for interleukin…
Figure 9
Representative immunohistochemical staining for interleukin (IL)-4 and IL-10. (A) Negative control (original magnification…
- The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups.Shapiro M, Green C, Faybush EM, Esquivel RF, Fass R. Shapiro M, et al. Aliment Pharmacol Ther. 2006 Jan 15;23(2):321-9. doi: 10.1111/j.1365-2036.2006.02747.x. Aliment Pharmacol Ther. 2006. PMID: 16393313
- Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?Frazzoni M, Manno M, De Micheli E, Savarino V. Frazzoni M, et al. Dig Liver Dis. 2006 Sep;38(9):643-8. doi: 10.1016/j.dld.2006.02.020. Epub 2006 Apr 14. Dig Liver Dis. 2006. PMID: 16627016
- Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Parrilla P, et al. Gut. 1990 Sep;31(9):964-7. doi: 10.1136/gut.31.9.964. Gut. 1990. PMID: 2210462 Free PMC article.
- Dyspepsia and Gastro-oesophageal Reflux: A Systematic Review [Internet].Swedish Council on Health Technology Assessment. Swedish Council on Health Technology Assessment. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. PMID: 28876800 Free Books & Documents. Review.
- Review article: management of oesophageal adenocarcinoma -- control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus.Jankowski JA, Anderson M. Jankowski JA, et al. Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:71-80; discussion 95-6. doi: 10.1111/j.1365-2036.2004.02143.x. Aliment Pharmacol Ther. 2004. PMID: 15456468 Review.
- Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.Zhang T, Zhang B, Tian W, Wei Y, Wang F, Yin X, Wei X, Liu J, Tang X. Zhang T, et al. Front Med (Lausanne). 2022 Sep 29;9:994534. doi: 10.3389/fmed.2022.994534. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36250094 Free PMC article.
- Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data.Morozov S, Sentsova T. Morozov S, et al. World J Clin Cases. 2022 Sep 16;10(26):9254-9263. doi: 10.12998/wjcc.v10.i26.9254. World J Clin Cases. 2022. PMID: 36159432 Free PMC article.
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?Zhang ML, Ran LQ, Wu MJ, Jia QC, Qin ZM, Peng YG. Zhang ML, et al. World J Clin Cases. 2022 Aug 26;10(24):8436-8442. doi: 10.12998/wjcc.v10.i24.8436. World J Clin Cases. 2022. PMID: 36157831 Free PMC article. Review.
- Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach.Sundaram S, Kim EN, Jones GM, Sivagnanam S, Tripathi M, Miremadi A, Di Pietro M, Coussens LM, Fitzgerald RC, Chang YH, Zhuang L. Sundaram S, et al. Front Immunol. 2022 May 19;13:874255. doi: 10.3389/fimmu.2022.874255. eCollection 2022. Front Immunol. 2022. PMID: 35663986 Free PMC article.
- Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?Borgmann M, Quante M. Borgmann M, et al. Cancers (Basel). 2022 Apr 30;14(9):2246. doi: 10.3390/cancers14092246. Cancers (Basel). 2022. PMID: 35565378 Free PMC article. Review.
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Barrett Esophagus / immunology*
- Cytokines / metabolism*
- Esophagitis / immunology*
- Female
- Gastroesophageal Reflux / immunology*
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Phenotype
- Prospective Studies
- RNA, Messenger / metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Th2 Cells / immunology*
- Cytokines
- RNA, Messenger
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f5.jpg)
Figure 6
Sample gels for interleukin (IL)-10…
Figure 6
Sample gels for interleukin (IL)-10 (A) and IL-4 (B). The amounts of synthetic…
Figure 7
Number of molecules of interferon…
Figure 7
Number of molecules of interferon γ (IFN-γ) and interleukin (IL)-4 as a ratio…
Figure 8
Representative examples of the cellular…
Figure 8
Representative examples of the cellular source of cytokine protein expression is shown by…
Figure 9
Representative immunohistochemical staining for interleukin…
Figure 9
Representative immunohistochemical staining for interleukin (IL)-4 and IL-10. (A) Negative control (original magnification…
- The extent of oesophageal acid exposure overlap among the different gastro-oesophageal reflux disease groups.Shapiro M, Green C, Faybush EM, Esquivel RF, Fass R. Shapiro M, et al. Aliment Pharmacol Ther. 2006 Jan 15;23(2):321-9. doi: 10.1111/j.1365-2036.2006.02747.x. Aliment Pharmacol Ther. 2006. PMID: 16393313
- Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?Frazzoni M, Manno M, De Micheli E, Savarino V. Frazzoni M, et al. Dig Liver Dis. 2006 Sep;38(9):643-8. doi: 10.1016/j.dld.2006.02.020. Epub 2006 Apr 14. Dig Liver Dis. 2006. PMID: 16627016
- Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus.Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Parrilla P, et al. Gut. 1990 Sep;31(9):964-7. doi: 10.1136/gut.31.9.964. Gut. 1990. PMID: 2210462 Free PMC article.
- Dyspepsia and Gastro-oesophageal Reflux: A Systematic Review [Internet].Swedish Council on Health Technology Assessment. Swedish Council on Health Technology Assessment. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2007 Oct. SBU Yellow Report No. 185. PMID: 28876800 Free Books & Documents. Review.
- Review article: management of oesophageal adenocarcinoma -- control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus.Jankowski JA, Anderson M. Jankowski JA, et al. Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:71-80; discussion 95-6. doi: 10.1111/j.1365-2036.2004.02143.x. Aliment Pharmacol Ther. 2004. PMID: 15456468 Review.
- Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.Zhang T, Zhang B, Tian W, Wei Y, Wang F, Yin X, Wei X, Liu J, Tang X. Zhang T, et al. Front Med (Lausanne). 2022 Sep 29;9:994534. doi: 10.3389/fmed.2022.994534. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36250094 Free PMC article.
- Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data.Morozov S, Sentsova T. Morozov S, et al. World J Clin Cases. 2022 Sep 16;10(26):9254-9263. doi: 10.12998/wjcc.v10.i26.9254. World J Clin Cases. 2022. PMID: 36159432 Free PMC article.
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?Zhang ML, Ran LQ, Wu MJ, Jia QC, Qin ZM, Peng YG. Zhang ML, et al. World J Clin Cases. 2022 Aug 26;10(24):8436-8442. doi: 10.12998/wjcc.v10.i24.8436. World J Clin Cases. 2022. PMID: 36157831 Free PMC article. Review.
- Deciphering the Immune Complexity in Esophageal Adenocarcinoma and Pre-Cancerous Lesions With Sequential Multiplex Immunohistochemistry and Sparse Subspace Clustering Approach.Sundaram S, Kim EN, Jones GM, Sivagnanam S, Tripathi M, Miremadi A, Di Pietro M, Coussens LM, Fitzgerald RC, Chang YH, Zhuang L. Sundaram S, et al. Front Immunol. 2022 May 19;13:874255. doi: 10.3389/fimmu.2022.874255. eCollection 2022. Front Immunol. 2022. PMID: 35663986 Free PMC article.
- Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?Borgmann M, Quante M. Borgmann M, et al. Cancers (Basel). 2022 Apr 30;14(9):2246. doi: 10.3390/cancers14092246. Cancers (Basel). 2022. PMID: 35565378 Free PMC article. Review.
- Research Support, Non-U.S. Gov't
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Barrett Esophagus / immunology*
- Cytokines / metabolism*
- Esophagitis / immunology*
- Female
- Gastroesophageal Reflux / immunology*
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Phenotype
- Prospective Studies
- RNA, Messenger / metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Th2 Cells / immunology*
- Cytokines
- RNA, Messenger
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f6.jpg)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f7.jpg)
Figure 8
Representative examples of the cellular…
Figure 8
Representative examples of the cellular source of cytokine protein expression is shown by…
Figure 9
Representative immunohistochemical staining for interleukin…
Figure 9
Representative immunohistochemical staining for interleukin (IL)-4 and IL-10. (A) Negative control (original magnification…
![Figure 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f8.jpg)
![Figure 9](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1773186/bin/0136.f9.jpg)
Source: PubMed