The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium
Background The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibi...
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| Veröffentlicht in: | International Journal of Obesity 2022-03, Vol.46 (3), p.605-612 |
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| creator | Naqvi, Anie MacKintosh, Michelle L. Derbyshire, Abigail E. Tsakiroglou, Anna-Maria Walker, Thomas D. J. McVey, Rhona J. Bolton, James Fergie, Martin Bagley, Steven Ashton, Garry Pemberton, Philip W. Syed, Akheel A. Ammori, Basil J. Byers, Richard Crosbie, Emma J. |
| description | Background
The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium.
Methods
We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2
) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss.
Results
Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2
, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (
n
= 37, median 63.3 kg) than low-calorie diet (
n
= 6, median 12.8 kg). There were significant reductions in serum CRP (
p
= 3.62 × 10
−6
,
r
= 0.570) and IL-6 (
p
= 0.0003,
r
= 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (
p
= 0.0097,
r
= −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (
p
= 0.0376;
r
= −0.318).
Conclusion
Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention. |
| doi_str_mv | 10.1038/s41366-021-01027-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8872994</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2606932189</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-f101a78a7054ad40aacc82023e10e267309bdf1ae76b45c29a13472e113aae1a3</originalsourceid><addsrcrecordid>eNp9kUtvFDEQhC0EIkvgD3BAlrhwGWg_xp65IKEoPKRIXMIRWT2ensTRjr3YM5H23-PshvA4cPKhvip3dzH2UsBbAap7V7RQxjQgRQMCpG3MI7YR2pqm1b19zDagwDbQmvaEPSvlBgDaFuRTdqJ019rOwoZ9v7wmHuYd-oWniaeBSlj2HOPIB8wBlxw8L2u-orznKfLlgM9rJD4HnxPF25BTnCke_HcyxTHNVI3r_Jw9mXBb6MX9e8q-fTy_PPvcXHz99OXsw0XjtdVLMwkQaDu00GocNSB630mQigSQNFZBP4yTQLJm0K2XPQqlrSQhFCIJVKfs_TF3tw4zjb5Ok3HrdjnMmPcuYXB_KzFcu6t067rOyr7XNeDNfUBOP1Yqi5tD8bTdYqS0FicNmF5J0fUVff0PepPWHOt6lVJSd7IHVSl5pOqNSsk0PQwjwN21547tudqeO7TnTDW9-nONB8uvuiqgjkCpUqyd_P77P7E_AZMrprA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2632482903</pqid></control><display><type>article</type><title>The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium</title><source>MEDLINE</source><source>Nature Journals Online</source><source>Alma/SFX Local Collection</source><creator>Naqvi, Anie ; MacKintosh, Michelle L. ; Derbyshire, Abigail E. ; Tsakiroglou, Anna-Maria ; Walker, Thomas D. J. ; McVey, Rhona J. ; Bolton, James ; Fergie, Martin ; Bagley, Steven ; Ashton, Garry ; Pemberton, Philip W. ; Syed, Akheel A. ; Ammori, Basil J. ; Byers, Richard ; Crosbie, Emma J.</creator><creatorcontrib>Naqvi, Anie ; MacKintosh, Michelle L. ; Derbyshire, Abigail E. ; Tsakiroglou, Anna-Maria ; Walker, Thomas D. J. ; McVey, Rhona J. ; Bolton, James ; Fergie, Martin ; Bagley, Steven ; Ashton, Garry ; Pemberton, Philip W. ; Syed, Akheel A. ; Ammori, Basil J. ; Byers, Richard ; Crosbie, Emma J.</creatorcontrib><description>Background
The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium.
Methods
We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2
) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss.
Results
Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2
, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (
n
= 37, median 63.3 kg) than low-calorie diet (
n
= 6, median 12.8 kg). There were significant reductions in serum CRP (
p
= 3.62 × 10
−6
,
r
= 0.570) and IL-6 (
p
= 0.0003,
r
= 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (
p
= 0.0097,
r
= −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (
p
= 0.0376;
r
= −0.318).
Conclusion
Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/s41366-021-01027-6</identifier><identifier>PMID: 34857870</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250 ; 631/67 ; 82 ; 82/51 ; Bariatric Surgery ; Biomarkers ; Body mass index ; Body size ; Body weight loss ; Cancer ; CD3 antigen ; CD56 antigen ; CD8 antigen ; Cell density ; Diet ; Endometrial cancer ; Endometrial Neoplasms - epidemiology ; Endometrium ; Endometrium - pathology ; Epidemiology ; Female ; Foxp3 protein ; Gastrointestinal surgery ; Health Promotion and Disease Prevention ; Health risks ; Humans ; Hypocaloric diet ; Immune system ; Immunofluorescence ; Immunology ; Immunosurveillance ; Inflammation ; Interleukin 6 ; Interleukin-6 - metabolism ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Microenvironments ; Nutrient deficiency ; Obesity ; Obesity - complications ; Obesity - surgery ; Paraffin ; Paraffins ; PD-1 protein ; Prospective Studies ; Public Health ; Surgery ; Tumor Microenvironment ; Tumor necrosis factor-α ; Weight control ; Weight Loss ; Weight loss measurement</subject><ispartof>International Journal of Obesity, 2022-03, Vol.46 (3), p.605-612</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-f101a78a7054ad40aacc82023e10e267309bdf1ae76b45c29a13472e113aae1a3</citedby><cites>FETCH-LOGICAL-c474t-f101a78a7054ad40aacc82023e10e267309bdf1ae76b45c29a13472e113aae1a3</cites><orcidid>0000-0002-9531-6109 ; 0000-0003-4607-7321 ; 0000-0002-9007-7292 ; 0000-0003-0284-8630</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34857870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naqvi, Anie</creatorcontrib><creatorcontrib>MacKintosh, Michelle L.</creatorcontrib><creatorcontrib>Derbyshire, Abigail E.</creatorcontrib><creatorcontrib>Tsakiroglou, Anna-Maria</creatorcontrib><creatorcontrib>Walker, Thomas D. J.</creatorcontrib><creatorcontrib>McVey, Rhona J.</creatorcontrib><creatorcontrib>Bolton, James</creatorcontrib><creatorcontrib>Fergie, Martin</creatorcontrib><creatorcontrib>Bagley, Steven</creatorcontrib><creatorcontrib>Ashton, Garry</creatorcontrib><creatorcontrib>Pemberton, Philip W.</creatorcontrib><creatorcontrib>Syed, Akheel A.</creatorcontrib><creatorcontrib>Ammori, Basil J.</creatorcontrib><creatorcontrib>Byers, Richard</creatorcontrib><creatorcontrib>Crosbie, Emma J.</creatorcontrib><title>The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description>Background
The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium.
Methods
We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2
) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss.
Results
Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2
, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (
n
= 37, median 63.3 kg) than low-calorie diet (
n
= 6, median 12.8 kg). There were significant reductions in serum CRP (
p
= 3.62 × 10
−6
,
r
= 0.570) and IL-6 (
p
= 0.0003,
r
= 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (
p
= 0.0097,
r
= −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (
p
= 0.0376;
r
= −0.318).
Conclusion
Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.</description><subject>631/250</subject><subject>631/67</subject><subject>82</subject><subject>82/51</subject><subject>Bariatric Surgery</subject><subject>Biomarkers</subject><subject>Body mass index</subject><subject>Body size</subject><subject>Body weight loss</subject><subject>Cancer</subject><subject>CD3 antigen</subject><subject>CD56 antigen</subject><subject>CD8 antigen</subject><subject>Cell density</subject><subject>Diet</subject><subject>Endometrial cancer</subject><subject>Endometrial Neoplasms - epidemiology</subject><subject>Endometrium</subject><subject>Endometrium - pathology</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Foxp3 protein</subject><subject>Gastrointestinal surgery</subject><subject>Health Promotion and Disease Prevention</subject><subject>Health risks</subject><subject>Humans</subject><subject>Hypocaloric diet</subject><subject>Immune system</subject><subject>Immunofluorescence</subject><subject>Immunology</subject><subject>Immunosurveillance</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - metabolism</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Microenvironments</subject><subject>Nutrient deficiency</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>Obesity - surgery</subject><subject>Paraffin</subject><subject>Paraffins</subject><subject>PD-1 protein</subject><subject>Prospective Studies</subject><subject>Public Health</subject><subject>Surgery</subject><subject>Tumor Microenvironment</subject><subject>Tumor necrosis factor-α</subject><subject>Weight control</subject><subject>Weight Loss</subject><subject>Weight loss measurement</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUtvFDEQhC0EIkvgD3BAlrhwGWg_xp65IKEoPKRIXMIRWT2ensTRjr3YM5H23-PshvA4cPKhvip3dzH2UsBbAap7V7RQxjQgRQMCpG3MI7YR2pqm1b19zDagwDbQmvaEPSvlBgDaFuRTdqJ019rOwoZ9v7wmHuYd-oWniaeBSlj2HOPIB8wBlxw8L2u-orznKfLlgM9rJD4HnxPF25BTnCke_HcyxTHNVI3r_Jw9mXBb6MX9e8q-fTy_PPvcXHz99OXsw0XjtdVLMwkQaDu00GocNSB630mQigSQNFZBP4yTQLJm0K2XPQqlrSQhFCIJVKfs_TF3tw4zjb5Ok3HrdjnMmPcuYXB_KzFcu6t067rOyr7XNeDNfUBOP1Yqi5tD8bTdYqS0FicNmF5J0fUVff0PepPWHOt6lVJSd7IHVSl5pOqNSsk0PQwjwN21547tudqeO7TnTDW9-nONB8uvuiqgjkCpUqyd_P77P7E_AZMrprA</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Naqvi, Anie</creator><creator>MacKintosh, Michelle L.</creator><creator>Derbyshire, Abigail E.</creator><creator>Tsakiroglou, Anna-Maria</creator><creator>Walker, Thomas D. J.</creator><creator>McVey, Rhona J.</creator><creator>Bolton, James</creator><creator>Fergie, Martin</creator><creator>Bagley, Steven</creator><creator>Ashton, Garry</creator><creator>Pemberton, Philip W.</creator><creator>Syed, Akheel A.</creator><creator>Ammori, Basil J.</creator><creator>Byers, Richard</creator><creator>Crosbie, Emma J.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7TS</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9531-6109</orcidid><orcidid>https://orcid.org/0000-0003-4607-7321</orcidid><orcidid>https://orcid.org/0000-0002-9007-7292</orcidid><orcidid>https://orcid.org/0000-0003-0284-8630</orcidid></search><sort><creationdate>20220301</creationdate><title>The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium</title><author>Naqvi, Anie ; MacKintosh, Michelle L. ; Derbyshire, Abigail E. ; Tsakiroglou, Anna-Maria ; Walker, Thomas D. J. ; McVey, Rhona J. ; Bolton, James ; Fergie, Martin ; Bagley, Steven ; Ashton, Garry ; Pemberton, Philip W. ; Syed, Akheel A. ; Ammori, Basil J. ; Byers, Richard ; Crosbie, Emma J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-f101a78a7054ad40aacc82023e10e267309bdf1ae76b45c29a13472e113aae1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>631/250</topic><topic>631/67</topic><topic>82</topic><topic>82/51</topic><topic>Bariatric Surgery</topic><topic>Biomarkers</topic><topic>Body mass index</topic><topic>Body size</topic><topic>Body weight loss</topic><topic>Cancer</topic><topic>CD3 antigen</topic><topic>CD56 antigen</topic><topic>CD8 antigen</topic><topic>Cell density</topic><topic>Diet</topic><topic>Endometrial cancer</topic><topic>Endometrial Neoplasms - epidemiology</topic><topic>Endometrium</topic><topic>Endometrium - pathology</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Foxp3 protein</topic><topic>Gastrointestinal surgery</topic><topic>Health Promotion and Disease Prevention</topic><topic>Health risks</topic><topic>Humans</topic><topic>Hypocaloric diet</topic><topic>Immune system</topic><topic>Immunofluorescence</topic><topic>Immunology</topic><topic>Immunosurveillance</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - metabolism</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Microenvironments</topic><topic>Nutrient deficiency</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>Obesity - surgery</topic><topic>Paraffin</topic><topic>Paraffins</topic><topic>PD-1 protein</topic><topic>Prospective Studies</topic><topic>Public Health</topic><topic>Surgery</topic><topic>Tumor Microenvironment</topic><topic>Tumor necrosis factor-α</topic><topic>Weight control</topic><topic>Weight Loss</topic><topic>Weight loss measurement</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naqvi, Anie</creatorcontrib><creatorcontrib>MacKintosh, Michelle L.</creatorcontrib><creatorcontrib>Derbyshire, Abigail E.</creatorcontrib><creatorcontrib>Tsakiroglou, Anna-Maria</creatorcontrib><creatorcontrib>Walker, Thomas D. J.</creatorcontrib><creatorcontrib>McVey, Rhona J.</creatorcontrib><creatorcontrib>Bolton, James</creatorcontrib><creatorcontrib>Fergie, Martin</creatorcontrib><creatorcontrib>Bagley, Steven</creatorcontrib><creatorcontrib>Ashton, Garry</creatorcontrib><creatorcontrib>Pemberton, Philip W.</creatorcontrib><creatorcontrib>Syed, Akheel A.</creatorcontrib><creatorcontrib>Ammori, Basil J.</creatorcontrib><creatorcontrib>Byers, Richard</creatorcontrib><creatorcontrib>Crosbie, Emma J.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International Journal of Obesity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naqvi, Anie</au><au>MacKintosh, Michelle L.</au><au>Derbyshire, Abigail E.</au><au>Tsakiroglou, Anna-Maria</au><au>Walker, Thomas D. J.</au><au>McVey, Rhona J.</au><au>Bolton, James</au><au>Fergie, Martin</au><au>Bagley, Steven</au><au>Ashton, Garry</au><au>Pemberton, Philip W.</au><au>Syed, Akheel A.</au><au>Ammori, Basil J.</au><au>Byers, Richard</au><au>Crosbie, Emma J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium</atitle><jtitle>International Journal of Obesity</jtitle><stitle>Int J Obes</stitle><addtitle>Int J Obes (Lond)</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>46</volume><issue>3</issue><spage>605</spage><epage>612</epage><pages>605-612</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><abstract>Background
The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium.
Methods
We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m
2
) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss.
Results
Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m
2
, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (
n
= 37, median 63.3 kg) than low-calorie diet (
n
= 6, median 12.8 kg). There were significant reductions in serum CRP (
p
= 3.62 × 10
−6
,
r
= 0.570) and IL-6 (
p
= 0.0003,
r
= 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (
p
= 0.0097,
r
= −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (
p
= 0.0376;
r
= −0.318).
Conclusion
Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34857870</pmid><doi>10.1038/s41366-021-01027-6</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9531-6109</orcidid><orcidid>https://orcid.org/0000-0003-4607-7321</orcidid><orcidid>https://orcid.org/0000-0002-9007-7292</orcidid><orcidid>https://orcid.org/0000-0003-0284-8630</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0307-0565 |
| ispartof | International Journal of Obesity, 2022-03, Vol.46 (3), p.605-612 |
| issn | 0307-0565 1476-5497 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8872994 |
| source | MEDLINE; Nature Journals Online; Alma/SFX Local Collection |
| subjects | 631/250 631/67 82 82/51 Bariatric Surgery Biomarkers Body mass index Body size Body weight loss Cancer CD3 antigen CD56 antigen CD8 antigen Cell density Diet Endometrial cancer Endometrial Neoplasms - epidemiology Endometrium Endometrium - pathology Epidemiology Female Foxp3 protein Gastrointestinal surgery Health Promotion and Disease Prevention Health risks Humans Hypocaloric diet Immune system Immunofluorescence Immunology Immunosurveillance Inflammation Interleukin 6 Interleukin-6 - metabolism Internal Medicine Male Medicine Medicine & Public Health Metabolic Diseases Microenvironments Nutrient deficiency Obesity Obesity - complications Obesity - surgery Paraffin Paraffins PD-1 protein Prospective Studies Public Health Surgery Tumor Microenvironment Tumor necrosis factor-α Weight control Weight Loss Weight loss measurement |
| title | The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T02%3A13%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20impact%20of%20obesity%20and%20bariatric%20surgery%20on%20the%20immune%20microenvironment%20of%20the%20endometrium&rft.jtitle=International%20Journal%20of%20Obesity&rft.au=Naqvi,%20Anie&rft.date=2022-03-01&rft.volume=46&rft.issue=3&rft.spage=605&rft.epage=612&rft.pages=605-612&rft.issn=0307-0565&rft.eissn=1476-5497&rft_id=info:doi/10.1038/s41366-021-01027-6&rft_dat=%3Cproquest_pubme%3E2606932189%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2632482903&rft_id=info:pmid/34857870&rfr_iscdi=true |