CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration
Non-small cell lung cancer (NSCLC) has a high incidence, with most patients diagnosed beyond the optimal surgical window. Improving survival rates is critical to reducing lung cancer mortality, and identifying immune checkpoints is vital for prognosis stratification. To investigate the expression of...
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| description | Non-small cell lung cancer (NSCLC) has a high incidence, with most patients diagnosed beyond the optimal surgical window. Improving survival rates is critical to reducing lung cancer mortality, and identifying immune checkpoints is vital for prognosis stratification.
To investigate the expression of CD47 in NSCLC and its relationship with tumor-associated macrophage infiltration.
A retrospective analysis was conducted on 50 NSCLC patients treated between January 2014 and June 2018. Immunohistochemistry and confocal microscopy assessed CD47 expression in tumor and adjacent tissues, while immunofluorescence evaluated CD47 on tumor-infiltrating T lymphocytes. Kaplan-Meier survival analysis and Cox regression identified prognostic factors, and PLA technology examined CD47's interaction with VEGFR and CD36.
CD47 positivity in tumor tissues (52%) was significantly higher than in adjacent tissues (20%) (P |
| doi_str_mv | 10.1371/journal.pone.0314228 |
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To investigate the expression of CD47 in NSCLC and its relationship with tumor-associated macrophage infiltration.
A retrospective analysis was conducted on 50 NSCLC patients treated between January 2014 and June 2018. Immunohistochemistry and confocal microscopy assessed CD47 expression in tumor and adjacent tissues, while immunofluorescence evaluated CD47 on tumor-infiltrating T lymphocytes. Kaplan-Meier survival analysis and Cox regression identified prognostic factors, and PLA technology examined CD47's interaction with VEGFR and CD36.
CD47 positivity in tumor tissues (52%) was significantly higher than in adjacent tissues (20%) (P<0.001), with expression localized to the cell membrane. CD47 expression correlated with lymph node metastasis, clinical stage, and differentiation (P<0.05) and was identified as an independent risk factor for poor prognosis. TAM infiltration was greater in CD47-positive patients and correlated with shorter survival (P<0.05). PLA showed stronger CD47+VEGFR interactions than CD47+CD36.
CD47 positivity correlates with poor prognosis and increased TAM infiltration, highlighting its potential as a prognostic biomarker and therapeutic target in NSCLC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0314228</identifier><identifier>PMID: 39652550</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Antibodies ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Body mass index ; Breast cancer ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - pathology ; Cardiovascular disease ; CD36 antigen ; CD47 Antigen - metabolism ; Cell differentiation ; Cell membranes ; Cell survival ; Cells ; Chemotherapy ; Confocal microscopy ; Correlation ; Female ; Gastric cancer ; Humans ; Immune checkpoint ; Immunofluorescence ; Immunohistochemistry ; Infiltration ; Kaplan-Meier Estimate ; Lung cancer ; Lung diseases ; Lung Neoplasms - metabolism ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Macrophages ; Male ; Medical prognosis ; Medicine and Health Sciences ; Metastases ; Middle Aged ; Mortality ; Non-small cell lung carcinoma ; Prognosis ; Research and Analysis Methods ; Retrospective Studies ; Risk factors ; Small cell lung carcinoma ; Smoking ; Stains & staining ; Surgery ; Survival ; Technology assessment ; Therapeutic targets ; Tumor-Associated Macrophages - immunology ; Tumor-Associated Macrophages - metabolism ; Tumor-Associated Macrophages - pathology ; Tumors ; Vascular endothelial growth factor receptors</subject><ispartof>PloS one, 2024, Vol.19 (12), p.e0314228</ispartof><rights>Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Zhang et al 2024 Zhang et al</rights><rights>2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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><orcidid>0000-0001-9830-1693</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627405/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627405/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,4024,23866,27923,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39652550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Hefeng</creatorcontrib><creatorcontrib>Liu, Shihu</creatorcontrib><creatorcontrib>Zhang, Jinzi</creatorcontrib><creatorcontrib>Wang, Yongjie</creatorcontrib><title>CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Non-small cell lung cancer (NSCLC) has a high incidence, with most patients diagnosed beyond the optimal surgical window. Improving survival rates is critical to reducing lung cancer mortality, and identifying immune checkpoints is vital for prognosis stratification.
To investigate the expression of CD47 in NSCLC and its relationship with tumor-associated macrophage infiltration.
A retrospective analysis was conducted on 50 NSCLC patients treated between January 2014 and June 2018. Immunohistochemistry and confocal microscopy assessed CD47 expression in tumor and adjacent tissues, while immunofluorescence evaluated CD47 on tumor-infiltrating T lymphocytes. Kaplan-Meier survival analysis and Cox regression identified prognostic factors, and PLA technology examined CD47's interaction with VEGFR and CD36.
CD47 positivity in tumor tissues (52%) was significantly higher than in adjacent tissues (20%) (P<0.001), with expression localized to the cell membrane. CD47 expression correlated with lymph node metastasis, clinical stage, and differentiation (P<0.05) and was identified as an independent risk factor for poor prognosis. TAM infiltration was greater in CD47-positive patients and correlated with shorter survival (P<0.05). PLA showed stronger CD47+VEGFR interactions than CD47+CD36.
CD47 positivity correlates with poor prognosis and increased TAM infiltration, highlighting its potential as a prognostic biomarker and therapeutic target in NSCLC.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Body mass index</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cardiovascular disease</subject><subject>CD36 antigen</subject><subject>CD47 Antigen - metabolism</subject><subject>Cell differentiation</subject><subject>Cell membranes</subject><subject>Cell survival</subject><subject>Cells</subject><subject>Chemotherapy</subject><subject>Confocal microscopy</subject><subject>Correlation</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Infiltration</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Non-small cell lung carcinoma</subject><subject>Prognosis</subject><subject>Research and Analysis Methods</subject><subject>Retrospective Studies</subject><subject>Risk factors</subject><subject>Small cell lung carcinoma</subject><subject>Smoking</subject><subject>Stains & staining</subject><subject>Surgery</subject><subject>Survival</subject><subject>Technology assessment</subject><subject>Therapeutic targets</subject><subject>Tumor-Associated Macrophages - immunology</subject><subject>Tumor-Associated Macrophages - metabolism</subject><subject>Tumor-Associated Macrophages - pathology</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUU1v1DAUtBCIloV_gMASFy5Z_JHYyQmh5atSJS5wtl7sl11XiR3spMC_x90uqEVc7Gd73nhmHiHPOdtyqfmbq7imAON2jgG3TPJaiPYBOeedFJUSTD68U5-RJzlfMdbIVqnH5Ex2qhFNw87JvHtfa4o_54Q5-xioDzTEUOUJxpFaLMu4hj21ECwmCsFRv2SacISlwPPBz_SHXw50WaeYKsg5Wg8LOjqBTXE-wB4L5-DHJR07npJHA4wZn532Dfn28cPX3efq8suni927y8oJrdoKHYNSdF0v5NDLcrQCFDYMUYmaAdOys06KpuNa8tYCDoMcZOOUHnqHrdyQl7e88xizOYWVzU1OxbjkqiAubhEuwpWZk58g_TIRvDlexLQ3kBZvRzROd6rXvWpt3dVdw6BGV0tXQwnUOc0K19vTb2s_obMYit3xHun9l-APZh-vDedK6LoMZkNenxhS_L5iXszk803-EDCuR-FKFddSF-irf6D_t_firqS_Wv7MXv4GRKaz8A</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Zhang, Hefeng</creator><creator>Liu, Shihu</creator><creator>Zhang, Jinzi</creator><creator>Wang, Yongjie</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9830-1693</orcidid></search><sort><creationdate>2024</creationdate><title>CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration</title><author>Zhang, Hefeng ; Liu, Shihu ; Zhang, Jinzi ; Wang, Yongjie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-d2768-ed0a27699b23fb3ed0c2a6e50ee6240a0739cd325917318caeff3f35d67fbde83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Body mass index</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cardiovascular disease</topic><topic>CD36 antigen</topic><topic>CD47 Antigen - metabolism</topic><topic>Cell differentiation</topic><topic>Cell membranes</topic><topic>Cell survival</topic><topic>Cells</topic><topic>Chemotherapy</topic><topic>Confocal microscopy</topic><topic>Correlation</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Infiltration</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung cancer</topic><topic>Lung diseases</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Non-small cell lung carcinoma</topic><topic>Prognosis</topic><topic>Research and Analysis Methods</topic><topic>Retrospective Studies</topic><topic>Risk factors</topic><topic>Small cell lung carcinoma</topic><topic>Smoking</topic><topic>Stains & staining</topic><topic>Surgery</topic><topic>Survival</topic><topic>Technology assessment</topic><topic>Therapeutic targets</topic><topic>Tumor-Associated Macrophages - immunology</topic><topic>Tumor-Associated Macrophages - metabolism</topic><topic>Tumor-Associated Macrophages - pathology</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Hefeng</creatorcontrib><creatorcontrib>Liu, Shihu</creatorcontrib><creatorcontrib>Zhang, Jinzi</creatorcontrib><creatorcontrib>Wang, Yongjie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</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>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Hefeng</au><au>Liu, Shihu</au><au>Zhang, Jinzi</au><au>Wang, Yongjie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024</date><risdate>2024</risdate><volume>19</volume><issue>12</issue><spage>e0314228</spage><pages>e0314228-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Non-small cell lung cancer (NSCLC) has a high incidence, with most patients diagnosed beyond the optimal surgical window. Improving survival rates is critical to reducing lung cancer mortality, and identifying immune checkpoints is vital for prognosis stratification.
To investigate the expression of CD47 in NSCLC and its relationship with tumor-associated macrophage infiltration.
A retrospective analysis was conducted on 50 NSCLC patients treated between January 2014 and June 2018. Immunohistochemistry and confocal microscopy assessed CD47 expression in tumor and adjacent tissues, while immunofluorescence evaluated CD47 on tumor-infiltrating T lymphocytes. Kaplan-Meier survival analysis and Cox regression identified prognostic factors, and PLA technology examined CD47's interaction with VEGFR and CD36.
CD47 positivity in tumor tissues (52%) was significantly higher than in adjacent tissues (20%) (P<0.001), with expression localized to the cell membrane. CD47 expression correlated with lymph node metastasis, clinical stage, and differentiation (P<0.05) and was identified as an independent risk factor for poor prognosis. TAM infiltration was greater in CD47-positive patients and correlated with shorter survival (P<0.05). PLA showed stronger CD47+VEGFR interactions than CD47+CD36.
CD47 positivity correlates with poor prognosis and increased TAM infiltration, highlighting its potential as a prognostic biomarker and therapeutic target in NSCLC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39652550</pmid><doi>10.1371/journal.pone.0314228</doi><orcidid>https://orcid.org/0000-0001-9830-1693</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Antibodies Biology and Life Sciences Biomarkers Biomarkers, Tumor - metabolism Body mass index Breast cancer Cancer therapies Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - pathology Cardiovascular disease CD36 antigen CD47 Antigen - metabolism Cell differentiation Cell membranes Cell survival Cells Chemotherapy Confocal microscopy Correlation Female Gastric cancer Humans Immune checkpoint Immunofluorescence Immunohistochemistry Infiltration Kaplan-Meier Estimate Lung cancer Lung diseases Lung Neoplasms - metabolism Lung Neoplasms - mortality Lung Neoplasms - pathology Lymph nodes Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Macrophages Male Medical prognosis Medicine and Health Sciences Metastases Middle Aged Mortality Non-small cell lung carcinoma Prognosis Research and Analysis Methods Retrospective Studies Risk factors Small cell lung carcinoma Smoking Stains & staining Surgery Survival Technology assessment Therapeutic targets Tumor-Associated Macrophages - immunology Tumor-Associated Macrophages - metabolism Tumor-Associated Macrophages - pathology Tumors Vascular endothelial growth factor receptors |
| title | CD47 expression in non-small cell lung cancer and its relationship with tumor-associated macrophage infiltration |
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