Reversed CD4/CD8 ratios of tumor‐infiltrating lymphocytes are correlated with the progression of human cervical carcinoma

BACKGROUND To investigate the clinical significance of tumor‐infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS A total of 30 patients with...

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Veröffentlicht in:Cancer 1999-10, Vol.86 (8), p.1537-1543
Hauptverfasser: Sheu, Bor‐Ching, Hsu, Su‐Ming, Ho, Hong‐Nerng, Lin, Rong‐Hwa, Torng, Pao‐Ling, Huang, Su‐Cheng
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container_end_page 1543
container_issue 8
container_start_page 1537
container_title Cancer
container_volume 86
creator Sheu, Bor‐Ching
Hsu, Su‐Ming
Ho, Hong‐Nerng
Lin, Rong‐Hwa
Torng, Pao‐Ling
Huang, Su‐Cheng
description BACKGROUND To investigate the clinical significance of tumor‐infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS A total of 30 patients with Stage Ia–IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual‐color flow cytometry. Bulky tumor was defined as tumor size >4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4+ T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4+ T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P < 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression. Cancer 1999;86:1537–43. © 1999 American Cancer Society. Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma patients.
doi_str_mv 10.1002/(SICI)1097-0142(19991015)86:8<1537::AID-CNCR21>3.0.CO;2-D
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METHODS A total of 30 patients with Stage Ia–IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual‐color flow cytometry. Bulky tumor was defined as tumor size &gt;4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4+ T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4+ T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P &lt; 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression. Cancer 1999;86:1537–43. © 1999 American Cancer Society. Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma patients.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/(SICI)1097-0142(19991015)86:8&lt;1537::AID-CNCR21&gt;3.0.CO;2-D</identifier><identifier>PMID: 10526283</identifier><language>eng</language><publisher>New York: John Wiley &amp; Sons, Inc</publisher><subject>Adenocarcinoma - immunology ; Adenocarcinoma - pathology ; AIDS/HIV ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - pathology ; CD4 Antigens - analysis ; CD4-CD8 Ratio ; CD8 Antigens - analysis ; cervical carcinoma ; Cervix ; Disease Progression ; Female ; Humans ; Immunophenotyping ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; lymph node metastasis ; Lymph Nodes - immunology ; Lymph Nodes - pathology ; Lymphatic Metastasis ; Lymphocyte Count ; Lymphocyte Subsets - cytology ; Lymphocyte Subsets - immunology ; Lymphocytes, Tumor-Infiltrating - cytology ; Lymphocytes, Tumor-Infiltrating - immunology ; Neoplasm Staging ; tumor‐infiltrating lymphocytes ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - pathology</subject><ispartof>Cancer, 1999-10, Vol.86 (8), p.1537-1543</ispartof><rights>Copyright © 1999 American Cancer Society</rights><rights>Copyright 1999 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4541-310c4b8e208c95084e6a9b9d88d4e9de9ccdc222d2de3f3aced857235527f55c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291097-0142%2819991015%2986%3A8%3C1537%3A%3AAID-CNCR21%3E3.0.CO%3B2-D$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291097-0142%2819991015%2986%3A8%3C1537%3A%3AAID-CNCR21%3E3.0.CO%3B2-D$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10526283$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheu, Bor‐Ching</creatorcontrib><creatorcontrib>Hsu, Su‐Ming</creatorcontrib><creatorcontrib>Ho, Hong‐Nerng</creatorcontrib><creatorcontrib>Lin, Rong‐Hwa</creatorcontrib><creatorcontrib>Torng, Pao‐Ling</creatorcontrib><creatorcontrib>Huang, Su‐Cheng</creatorcontrib><title>Reversed CD4/CD8 ratios of tumor‐infiltrating lymphocytes are correlated with the progression of human cervical carcinoma</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND To investigate the clinical significance of tumor‐infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS A total of 30 patients with Stage Ia–IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual‐color flow cytometry. Bulky tumor was defined as tumor size &gt;4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4+ T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4+ T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P &lt; 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression. Cancer 1999;86:1537–43. © 1999 American Cancer Society. Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma patients.</description><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - pathology</subject><subject>AIDS/HIV</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>CD4 Antigens - analysis</subject><subject>CD4-CD8 Ratio</subject><subject>CD8 Antigens - analysis</subject><subject>cervical carcinoma</subject><subject>Cervix</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - immunology</subject><subject>lymph node metastasis</subject><subject>Lymph Nodes - immunology</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Lymphocyte Count</subject><subject>Lymphocyte Subsets - cytology</subject><subject>Lymphocyte Subsets - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - cytology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Neoplasm Staging</subject><subject>tumor‐infiltrating lymphocytes</subject><subject>Uterine Cervical Neoplasms - immunology</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-K00AUxgdR3Fp9BZkr2b1Id_5kkpkqQklXLSwWVgXFi8N0crKN5E-dSXYpe-Mj-Iw-iQmtIih4NczhO993-H6ELDibccbE-em7VbY648ykEeOxOOXGGM64OtPJXL_gSqbz-WK1jLK32ZXgL-WMzbL1cxEt75HJ7637ZMIY05GK5ccT8iiEL8M3FUo-JCecKZEILSfk7gpv0AfMabaMz7Olpt52ZRtoW9Cur1v_49v3sinKqhvnzTWt9vVu27p9h4Faj9S13mNlu8Hhtuy2tNsi3fn22mMIZduMPtu-tg116G9KZyvqrHdl09b2MXlQ2Crgk-M7JR9eXbzP3kSX69erbHEZuVjFPJKcuXijUTDtjGI6xsSajcm1zmM0ORrncieEyEWOspDWYa5VKqRSIi2UcnJKnh18h7u-9hg6qMvgsKpsg20fIDFCpGZoZko-HYTOtyF4LGDny9r6PXAGIxmAkQyMHcPYMfwiAzoBDSMZgIEMHMiABAbZGgQsB--nxyP6TY35H84HFIPg80FwW1a4_yv5_8H_zD1O5E8P_a27</recordid><startdate>19991015</startdate><enddate>19991015</enddate><creator>Sheu, Bor‐Ching</creator><creator>Hsu, Su‐Ming</creator><creator>Ho, Hong‐Nerng</creator><creator>Lin, Rong‐Hwa</creator><creator>Torng, Pao‐Ling</creator><creator>Huang, Su‐Cheng</creator><general>John Wiley &amp; Sons, Inc</general><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>7X8</scope></search><sort><creationdate>19991015</creationdate><title>Reversed CD4/CD8 ratios of tumor‐infiltrating lymphocytes are correlated with the progression of human cervical carcinoma</title><author>Sheu, Bor‐Ching ; Hsu, Su‐Ming ; Ho, Hong‐Nerng ; Lin, Rong‐Hwa ; Torng, Pao‐Ling ; Huang, Su‐Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4541-310c4b8e208c95084e6a9b9d88d4e9de9ccdc222d2de3f3aced857235527f55c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - pathology</topic><topic>AIDS/HIV</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>CD4 Antigens - analysis</topic><topic>CD4-CD8 Ratio</topic><topic>CD8 Antigens - analysis</topic><topic>cervical carcinoma</topic><topic>Cervix</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Killer Cells, Natural - cytology</topic><topic>Killer Cells, Natural - immunology</topic><topic>lymph node metastasis</topic><topic>Lymph Nodes - immunology</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Lymphocyte Count</topic><topic>Lymphocyte Subsets - cytology</topic><topic>Lymphocyte Subsets - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - cytology</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Neoplasm Staging</topic><topic>tumor‐infiltrating lymphocytes</topic><topic>Uterine Cervical Neoplasms - immunology</topic><topic>Uterine Cervical Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sheu, Bor‐Ching</creatorcontrib><creatorcontrib>Hsu, Su‐Ming</creatorcontrib><creatorcontrib>Ho, Hong‐Nerng</creatorcontrib><creatorcontrib>Lin, Rong‐Hwa</creatorcontrib><creatorcontrib>Torng, Pao‐Ling</creatorcontrib><creatorcontrib>Huang, Su‐Cheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sheu, Bor‐Ching</au><au>Hsu, Su‐Ming</au><au>Ho, Hong‐Nerng</au><au>Lin, Rong‐Hwa</au><au>Torng, Pao‐Ling</au><au>Huang, Su‐Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversed CD4/CD8 ratios of tumor‐infiltrating lymphocytes are correlated with the progression of human cervical carcinoma</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>1999-10-15</date><risdate>1999</risdate><volume>86</volume><issue>8</issue><spage>1537</spage><epage>1543</epage><pages>1537-1543</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>BACKGROUND To investigate the clinical significance of tumor‐infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, the authors quantitatively measured and compared the subpopulations of lymphocytes infiltrating the neoplastic cervix. METHODS A total of 30 patients with Stage Ia–IIa cervical carcinoma were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique, and the immunocyte subsets were quantified with dual‐color flow cytometry. Bulky tumor was defined as tumor size &gt;4 cm in greatest dimension according to the 1995 staging of the International Federation of Gynecology and Obstetrics. RESULTS The CD4/CD8 ratios of TILs were reversed in both cervical squamous cell carcinoma (n = 20) and cervical adenocarcinoma (n = 10). The proportion of CD4+ T cells was significantly lower in tumors from patients with lymph node metastasis (n = 8) than in those from patients without lymph node metastasis (n = 22) (24.5 vs. 32.7, P = 0.001), as was the reversed CD4/CD8 ratio (0.50 vs. 0.81, P = 0.001). The proportion of CD4+ T cells was much lower in bulky tumors (n = 5) than in nonbulky tumors (n = 25) (21.4 vs. 32.5, P &lt; 0.001), reflecting in a more strongly reversed CD4/CD8 ratio (0.41 vs. 0.81, P = 0.001). CONCLUSIONS Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma. The regional immune escape is of prognostic importance with regard to cancer progression. Cancer 1999;86:1537–43. © 1999 American Cancer Society. Decreased proportions of tumor‐infiltrating CD4+ T cells with reversed CD4/CD8 ratios are highly correlated with rapid tumor growth and lymph node metastasis in cervical carcinoma patients.</abstract><cop>New York</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>10526283</pmid><doi>10.1002/(SICI)1097-0142(19991015)86:8&lt;1537::AID-CNCR21&gt;3.0.CO;2-D</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adenocarcinoma - immunology
Adenocarcinoma - pathology
AIDS/HIV
Carcinoma, Squamous Cell - immunology
Carcinoma, Squamous Cell - pathology
CD4 Antigens - analysis
CD4-CD8 Ratio
CD8 Antigens - analysis
cervical carcinoma
Cervix
Disease Progression
Female
Humans
Immunophenotyping
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
lymph node metastasis
Lymph Nodes - immunology
Lymph Nodes - pathology
Lymphatic Metastasis
Lymphocyte Count
Lymphocyte Subsets - cytology
Lymphocyte Subsets - immunology
Lymphocytes, Tumor-Infiltrating - cytology
Lymphocytes, Tumor-Infiltrating - immunology
Neoplasm Staging
tumor‐infiltrating lymphocytes
Uterine Cervical Neoplasms - immunology
Uterine Cervical Neoplasms - pathology
title Reversed CD4/CD8 ratios of tumor‐infiltrating lymphocytes are correlated with the progression of human cervical carcinoma
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