Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma
CD28, one of the costimulatory molecules, has a pivotal role in T‐cell activation, and its expression is strictly regulated in normal T cells. Gain‐of‐function genetic alterations involving CD28 have been frequently observed in adult T‐cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28...
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| Veröffentlicht in: | Cancer science 2022-01, Vol.113 (1), p.349-361 |
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| creator | Sakamoto, Yuma Ishida, Takashi Masaki, Ayako Takeshita, Morishige Iwasaki, Hiromi Yonekura, Kentaro Tashiro, Yukie Ito, Asahi Kusumoto, Shigeru Iida, Shinsuke Utsunomiya, Atae Ueda, Ryuzo Inagaki, Hiroshi |
| description | CD28, one of the costimulatory molecules, has a pivotal role in T‐cell activation, and its expression is strictly regulated in normal T cells. Gain‐of‐function genetic alterations involving CD28 have been frequently observed in adult T‐cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non‐overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86‐positive non‐neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non‐overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
The aim of the present study was to determine the clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma (ATLL). CD28 overexpression is associated with unfavorable prognosis of ATLL patients who were treated with multidrug regimens including mogamulizumab; thus, CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL. |
| doi_str_mv | 10.1111/cas.15191 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8748252</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2618380014</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4671-888d020b926d05c7f64ea5508f7775c46696dcc100d2d9025a6803f38958ca6a3</originalsourceid><addsrcrecordid>eNp1kUtuFDEQhi0EIiGw4AKoJTaw6EzZbr82SFHzlCKxIKxYWI7bPePgtht7OjA7jsAZOQlOJkSARG2qZH_6VKUfoccYjnGtlTXlGDOs8B10iGmnWgHA717PolVAyQF6UMoFAOWd6u6jg_pOpQBxiD71wUdv02y2mxTS2lsTmuLX0Y91jNY1aWz6l0Q26dJl923OrhSfYuNjY4YlbJuzn99_WBdCE9zy2U3erMJumjdpMg_RvdGE4h7d9CP08fWrs_5te_r-zbv-5LS1HRe4lVIOQOBcET4As2LknTOMgRyFEKwyXPHBWgwwkEEBYYZLoCOViklruKFH6MXeOy_nkxusi9tsgp6zn0ze6WS8_vsn-o1ep0stRScJI1Xw7EaQ05fFla2efLm6yUSXlqIJUx1RQlFR0af_oBdpybGepwnHkkoA3FXq-Z6yOZWS3Xi7DAZ9FZmukenryCr75M_tb8nfGVVgtQe--uB2_zfp_uTDXvkL5E-hKw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2618380014</pqid></control><display><type>article</type><title>Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma</title><source>MEDLINE</source><source>Wiley-Blackwell Open Access Titles</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Sakamoto, Yuma ; Ishida, Takashi ; Masaki, Ayako ; Takeshita, Morishige ; Iwasaki, Hiromi ; Yonekura, Kentaro ; Tashiro, Yukie ; Ito, Asahi ; Kusumoto, Shigeru ; Iida, Shinsuke ; Utsunomiya, Atae ; Ueda, Ryuzo ; Inagaki, Hiroshi</creator><creatorcontrib>Sakamoto, Yuma ; Ishida, Takashi ; Masaki, Ayako ; Takeshita, Morishige ; Iwasaki, Hiromi ; Yonekura, Kentaro ; Tashiro, Yukie ; Ito, Asahi ; Kusumoto, Shigeru ; Iida, Shinsuke ; Utsunomiya, Atae ; Ueda, Ryuzo ; Inagaki, Hiroshi</creatorcontrib><description>CD28, one of the costimulatory molecules, has a pivotal role in T‐cell activation, and its expression is strictly regulated in normal T cells. Gain‐of‐function genetic alterations involving CD28 have been frequently observed in adult T‐cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non‐overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86‐positive non‐neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non‐overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
The aim of the present study was to determine the clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma (ATLL). CD28 overexpression is associated with unfavorable prognosis of ATLL patients who were treated with multidrug regimens including mogamulizumab; thus, CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.15191</identifier><identifier>PMID: 34738707</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adult ; adult T‐cell leukemia/lymphoma ; Aged ; Aged, 80 and over ; Antigens ; B7-1 Antigen - metabolism ; B7-2 Antigen - metabolism ; CD28 ; CD28 antigen ; CD28 Antigens - genetics ; CD28 Antigens - metabolism ; CD80 (B7‐1) ; CD80 antigen ; CD86 (B7‐2) ; CD86 antigen ; Cell activation ; Chemotherapy ; Cloning ; Copy number ; Costimulator ; costimulatory molecule ; Cytokines ; Cytotoxicity ; DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic ; genetic alterations ; Hematopoietic stem cells ; Hemoglobin ; Humans ; Immunohistochemistry ; Leukemia ; Leukemia-Lymphoma, Adult T-Cell - genetics ; Leukemia-Lymphoma, Adult T-Cell - metabolism ; Leukemia-Lymphoma, Adult T-Cell - mortality ; Lymphocytes ; Lymphocytes T ; Lymphoma ; Male ; Medical prognosis ; Middle Aged ; Monoclonal antibodies ; Multivariate analysis ; Mutation ; Original ; overexpression ; Patients ; Prognosis ; Protein expression ; Risk factors ; Stem cell transplantation ; Survival Analysis ; Tumor cells ; Tumor Microenvironment ; Tumor-infiltrating lymphocytes ; Up-Regulation</subject><ispartof>Cancer science, 2022-01, Vol.113 (1), p.349-361</ispartof><rights>2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/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-c4671-888d020b926d05c7f64ea5508f7775c46696dcc100d2d9025a6803f38958ca6a3</citedby><cites>FETCH-LOGICAL-c4671-888d020b926d05c7f64ea5508f7775c46696dcc100d2d9025a6803f38958ca6a3</cites><orcidid>0000-0001-9916-4862 ; 0000-0002-4951-960X ; 0000-0001-6157-636X ; 0000-0002-1060-0777</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/PMC8748252/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748252/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34738707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakamoto, Yuma</creatorcontrib><creatorcontrib>Ishida, Takashi</creatorcontrib><creatorcontrib>Masaki, Ayako</creatorcontrib><creatorcontrib>Takeshita, Morishige</creatorcontrib><creatorcontrib>Iwasaki, Hiromi</creatorcontrib><creatorcontrib>Yonekura, Kentaro</creatorcontrib><creatorcontrib>Tashiro, Yukie</creatorcontrib><creatorcontrib>Ito, Asahi</creatorcontrib><creatorcontrib>Kusumoto, Shigeru</creatorcontrib><creatorcontrib>Iida, Shinsuke</creatorcontrib><creatorcontrib>Utsunomiya, Atae</creatorcontrib><creatorcontrib>Ueda, Ryuzo</creatorcontrib><creatorcontrib>Inagaki, Hiroshi</creatorcontrib><title>Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>CD28, one of the costimulatory molecules, has a pivotal role in T‐cell activation, and its expression is strictly regulated in normal T cells. Gain‐of‐function genetic alterations involving CD28 have been frequently observed in adult T‐cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non‐overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86‐positive non‐neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non‐overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
The aim of the present study was to determine the clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma (ATLL). CD28 overexpression is associated with unfavorable prognosis of ATLL patients who were treated with multidrug regimens including mogamulizumab; thus, CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL.</description><subject>Adult</subject><subject>adult T‐cell leukemia/lymphoma</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens</subject><subject>B7-1 Antigen - metabolism</subject><subject>B7-2 Antigen - metabolism</subject><subject>CD28</subject><subject>CD28 antigen</subject><subject>CD28 Antigens - genetics</subject><subject>CD28 Antigens - metabolism</subject><subject>CD80 (B7‐1)</subject><subject>CD80 antigen</subject><subject>CD86 (B7‐2)</subject><subject>CD86 antigen</subject><subject>Cell activation</subject><subject>Chemotherapy</subject><subject>Cloning</subject><subject>Copy number</subject><subject>Costimulator</subject><subject>costimulatory molecule</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>DNA Copy Number Variations</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>genetic alterations</subject><subject>Hematopoietic stem cells</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Leukemia</subject><subject>Leukemia-Lymphoma, Adult T-Cell - genetics</subject><subject>Leukemia-Lymphoma, Adult T-Cell - metabolism</subject><subject>Leukemia-Lymphoma, Adult T-Cell - mortality</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Original</subject><subject>overexpression</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Risk factors</subject><subject>Stem cell transplantation</subject><subject>Survival Analysis</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment</subject><subject>Tumor-infiltrating lymphocytes</subject><subject>Up-Regulation</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtuFDEQhi0EIiGw4AKoJTaw6EzZbr82SFHzlCKxIKxYWI7bPePgtht7OjA7jsAZOQlOJkSARG2qZH_6VKUfoccYjnGtlTXlGDOs8B10iGmnWgHA717PolVAyQF6UMoFAOWd6u6jg_pOpQBxiD71wUdv02y2mxTS2lsTmuLX0Y91jNY1aWz6l0Q26dJl923OrhSfYuNjY4YlbJuzn99_WBdCE9zy2U3erMJumjdpMg_RvdGE4h7d9CP08fWrs_5te_r-zbv-5LS1HRe4lVIOQOBcET4As2LknTOMgRyFEKwyXPHBWgwwkEEBYYZLoCOViklruKFH6MXeOy_nkxusi9tsgp6zn0ze6WS8_vsn-o1ep0stRScJI1Xw7EaQ05fFla2efLm6yUSXlqIJUx1RQlFR0af_oBdpybGepwnHkkoA3FXq-Z6yOZWS3Xi7DAZ9FZmukenryCr75M_tb8nfGVVgtQe--uB2_zfp_uTDXvkL5E-hKw</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Sakamoto, Yuma</creator><creator>Ishida, Takashi</creator><creator>Masaki, Ayako</creator><creator>Takeshita, Morishige</creator><creator>Iwasaki, Hiromi</creator><creator>Yonekura, Kentaro</creator><creator>Tashiro, Yukie</creator><creator>Ito, Asahi</creator><creator>Kusumoto, Shigeru</creator><creator>Iida, Shinsuke</creator><creator>Utsunomiya, Atae</creator><creator>Ueda, Ryuzo</creator><creator>Inagaki, Hiroshi</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9916-4862</orcidid><orcidid>https://orcid.org/0000-0002-4951-960X</orcidid><orcidid>https://orcid.org/0000-0001-6157-636X</orcidid><orcidid>https://orcid.org/0000-0002-1060-0777</orcidid></search><sort><creationdate>202201</creationdate><title>Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma</title><author>Sakamoto, Yuma ; Ishida, Takashi ; Masaki, Ayako ; Takeshita, Morishige ; Iwasaki, Hiromi ; Yonekura, Kentaro ; Tashiro, Yukie ; Ito, Asahi ; Kusumoto, Shigeru ; Iida, Shinsuke ; Utsunomiya, Atae ; Ueda, Ryuzo ; Inagaki, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4671-888d020b926d05c7f64ea5508f7775c46696dcc100d2d9025a6803f38958ca6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>adult T‐cell leukemia/lymphoma</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens</topic><topic>B7-1 Antigen - metabolism</topic><topic>B7-2 Antigen - metabolism</topic><topic>CD28</topic><topic>CD28 antigen</topic><topic>CD28 Antigens - genetics</topic><topic>CD28 Antigens - metabolism</topic><topic>CD80 (B7‐1)</topic><topic>CD80 antigen</topic><topic>CD86 (B7‐2)</topic><topic>CD86 antigen</topic><topic>Cell activation</topic><topic>Chemotherapy</topic><topic>Cloning</topic><topic>Copy number</topic><topic>Costimulator</topic><topic>costimulatory molecule</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>DNA Copy Number Variations</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>genetic alterations</topic><topic>Hematopoietic stem cells</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Leukemia</topic><topic>Leukemia-Lymphoma, Adult T-Cell - genetics</topic><topic>Leukemia-Lymphoma, Adult T-Cell - metabolism</topic><topic>Leukemia-Lymphoma, Adult T-Cell - mortality</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Original</topic><topic>overexpression</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Risk factors</topic><topic>Stem cell transplantation</topic><topic>Survival Analysis</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment</topic><topic>Tumor-infiltrating lymphocytes</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakamoto, Yuma</creatorcontrib><creatorcontrib>Ishida, Takashi</creatorcontrib><creatorcontrib>Masaki, Ayako</creatorcontrib><creatorcontrib>Takeshita, Morishige</creatorcontrib><creatorcontrib>Iwasaki, Hiromi</creatorcontrib><creatorcontrib>Yonekura, Kentaro</creatorcontrib><creatorcontrib>Tashiro, Yukie</creatorcontrib><creatorcontrib>Ito, Asahi</creatorcontrib><creatorcontrib>Kusumoto, Shigeru</creatorcontrib><creatorcontrib>Iida, Shinsuke</creatorcontrib><creatorcontrib>Utsunomiya, Atae</creatorcontrib><creatorcontrib>Ueda, Ryuzo</creatorcontrib><creatorcontrib>Inagaki, Hiroshi</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</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 SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakamoto, Yuma</au><au>Ishida, Takashi</au><au>Masaki, Ayako</au><au>Takeshita, Morishige</au><au>Iwasaki, Hiromi</au><au>Yonekura, Kentaro</au><au>Tashiro, Yukie</au><au>Ito, Asahi</au><au>Kusumoto, Shigeru</au><au>Iida, Shinsuke</au><au>Utsunomiya, Atae</au><au>Ueda, Ryuzo</au><au>Inagaki, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2022-01</date><risdate>2022</risdate><volume>113</volume><issue>1</issue><spage>349</spage><epage>361</epage><pages>349-361</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>CD28, one of the costimulatory molecules, has a pivotal role in T‐cell activation, and its expression is strictly regulated in normal T cells. Gain‐of‐function genetic alterations involving CD28 have been frequently observed in adult T‐cell leukemia/lymphoma (ATLL). These abnormalities, such as CD28 fusions and copy number variations, may not only confer continuous, prolonged, and enhanced CD28 signaling to downstream pathways but also induce overexpression of the CD28 protein. In this study, 120 ATLL cases were examined by immunohistochemistry for CD28 and its ligands CD80 and CD86, and their expression on tumor cells was semiquantitatively evaluated. CD28 was overexpressed in 55 (46%) cases, and CD80 or CD86 (CD80/CD86) was infrequently overexpressed in 12 (11%). Compared with non‐overexpressers, CD28 overexpressers showed a higher frequency of CD28 genetic alterations and had an increased number of CD80/CD86‐positive non‐neoplastic cells infiltrating tumor microenvironment. In the entire ATLL patient cohort, CD28 overexpressers showed a significantly poorer overall survival (OS) compared with non‐overexpressers (P = .001). The same was true for a subgroup who were treated with multidrug regimens with or without mogamulizumab. CD28 overexpression had no prognostic impact in the group who received allogeneic hematopoietic stem cell transplantation. In the multivariate analysis for OS, CD28 overexpression was selected as an independent risk factor. These results suggest ATLL patients with CD28 overexpression have more aggressive clinical course and are more refractory to treatment with multidrug chemotherapy. CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL patients, and further prospective studies are warranted to establish its prognostic significance.
The aim of the present study was to determine the clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma (ATLL). CD28 overexpression is associated with unfavorable prognosis of ATLL patients who were treated with multidrug regimens including mogamulizumab; thus, CD28 overexpression appears to be a novel unfavorable prognostic marker in ATLL.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34738707</pmid><doi>10.1111/cas.15191</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9916-4862</orcidid><orcidid>https://orcid.org/0000-0002-4951-960X</orcidid><orcidid>https://orcid.org/0000-0001-6157-636X</orcidid><orcidid>https://orcid.org/0000-0002-1060-0777</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2022-01, Vol.113 (1), p.349-361 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8748252 |
| source | MEDLINE; Wiley-Blackwell Open Access Titles; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Adult adult T‐cell leukemia/lymphoma Aged Aged, 80 and over Antigens B7-1 Antigen - metabolism B7-2 Antigen - metabolism CD28 CD28 antigen CD28 Antigens - genetics CD28 Antigens - metabolism CD80 (B7‐1) CD80 antigen CD86 (B7‐2) CD86 antigen Cell activation Chemotherapy Cloning Copy number Costimulator costimulatory molecule Cytokines Cytotoxicity DNA Copy Number Variations Female Gene Expression Regulation, Neoplastic genetic alterations Hematopoietic stem cells Hemoglobin Humans Immunohistochemistry Leukemia Leukemia-Lymphoma, Adult T-Cell - genetics Leukemia-Lymphoma, Adult T-Cell - metabolism Leukemia-Lymphoma, Adult T-Cell - mortality Lymphocytes Lymphocytes T Lymphoma Male Medical prognosis Middle Aged Monoclonal antibodies Multivariate analysis Mutation Original overexpression Patients Prognosis Protein expression Risk factors Stem cell transplantation Survival Analysis Tumor cells Tumor Microenvironment Tumor-infiltrating lymphocytes Up-Regulation |
| title | Clinicopathological significance of CD28 overexpression in adult T‐cell leukemia/lymphoma |
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