B7-H4 Expression in Renal Cell Carcinoma and Tumor Vasculature: Associations with Cancer Progression and Survival
B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (27), p.10391-10396 |
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| creator | Krambeck, Amy E. Thompson, R. Houston Dong, Haidong Lohse, Christine M. Park, Eugene S. Kuntz, Susan M. Leibovich, Bradley C. Blute, Michael L. Cheville, John C. Kwon, Eugene D. |
| description | B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC. |
| doi_str_mv | 10.1073/pnas.0600937103 |
| format | Article |
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Houston ; Dong, Haidong ; Lohse, Christine M. ; Park, Eugene S. ; Kuntz, Susan M. ; Leibovich, Bradley C. ; Blute, Michael L. ; Cheville, John C. ; Kwon, Eugene D.</creator><creatorcontrib>Krambeck, Amy E. ; Thompson, R. Houston ; Dong, Haidong ; Lohse, Christine M. ; Park, Eugene S. ; Kuntz, Susan M. ; Leibovich, Bradley C. ; Blute, Michael L. ; Cheville, John C. ; Kwon, Eugene D.</creatorcontrib><description>B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0600937103</identifier><identifier>PMID: 16798883</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Aged ; Antigens, CD - metabolism ; B7-1 Antigen - metabolism ; B7-H1 Antigen ; Biological Sciences ; Cancer ; Carcinoma, Renal Cell - blood supply ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; Carcinoma, Renal Cell - surgery ; Cardiovascular system ; Cells ; Disease Progression ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy ; Kidneys ; Male ; Middle Aged ; Nephrectomy ; Nephrology ; Pathology ; Renal cell carcinoma ; Specimens ; Survival Rate ; Survival rates ; T lymphocytes ; Treatment Outcome ; Tumors ; V-Set Domain-Containing T-Cell Activation Inhibitor 1</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2006-07, Vol.103 (27), p.10391-10396</ispartof><rights>Copyright 2006 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jul 5, 2006</rights><rights>2006 by The National Academy of Sciences of the USA 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-c0dcb9f268a7f8c0d1972fbb002bf8db5d36e2c1ce34910b932bf3d97858bab43</citedby><cites>FETCH-LOGICAL-c530t-c0dcb9f268a7f8c0d1972fbb002bf8db5d36e2c1ce34910b932bf3d97858bab43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/103/27.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30049634$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30049634$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53770,53772,57996,58229</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16798883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krambeck, Amy E.</creatorcontrib><creatorcontrib>Thompson, R. Houston</creatorcontrib><creatorcontrib>Dong, Haidong</creatorcontrib><creatorcontrib>Lohse, Christine M.</creatorcontrib><creatorcontrib>Park, Eugene S.</creatorcontrib><creatorcontrib>Kuntz, Susan M.</creatorcontrib><creatorcontrib>Leibovich, Bradley C.</creatorcontrib><creatorcontrib>Blute, Michael L.</creatorcontrib><creatorcontrib>Cheville, John C.</creatorcontrib><creatorcontrib>Kwon, Eugene D.</creatorcontrib><title>B7-H4 Expression in Renal Cell Carcinoma and Tumor Vasculature: Associations with Cancer Progression and Survival</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.</description><subject>Aged</subject><subject>Antigens, CD - metabolism</subject><subject>B7-1 Antigen - metabolism</subject><subject>B7-H1 Antigen</subject><subject>Biological Sciences</subject><subject>Cancer</subject><subject>Carcinoma, Renal Cell - blood supply</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Carcinoma, Renal Cell - surgery</subject><subject>Cardiovascular system</subject><subject>Cells</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Kidneys</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nephrectomy</subject><subject>Nephrology</subject><subject>Pathology</subject><subject>Renal cell carcinoma</subject><subject>Specimens</subject><subject>Survival Rate</subject><subject>Survival rates</subject><subject>T lymphocytes</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>V-Set Domain-Containing T-Cell Activation Inhibitor 1</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EotvCmRPI4lCJQ9px7PiDA1JZFYpUCQSFq-U4TutVEm_tZCn_PY526QKXXjyy_XtPM_MQekHghICgp-vBpBPgAIoKAvQRWhBQpOBMwWO0AChFIVnJDtBhSivIWCXhKTogXCgpJV2g2_eiuGD4_G4dXUo-DNgP-KsbTIeXrsuHidYPoTfYDA2-mvoQ8Q-T7NSZcYruLT5LKVhvxixN-Kcfb7JksC7iLzFc__Gctd-muPEb0z1DT1rTJfd8V4_Q9w_nV8uL4vLzx0_Ls8vCVhTGwkJja9WWXBrRynwjSpRtXeeZ6lY2ddVQ7kpLrKNMEagVze-0UUJWsjY1o0fo3dZ3PdW9a6wbxmg6vY6-N_GXDsbrf38Gf6Ovw0aTCkrGZTY43hnEcDu5NOreJ5uXYgYXpqS55IQSCg-CRJQclKoy-Po_cBWmmHeddAmEEVKJue_TLWRjSCm69r5lAnoOXc-h633oWfHq70n3_C7lDOAdMCv3dlSXYi6KZOTNA4hup64b3d2Y2ZdbdpXGEO9hCsAUp4z-BqsPy70</recordid><startdate>20060705</startdate><enddate>20060705</enddate><creator>Krambeck, Amy E.</creator><creator>Thompson, R. 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Houston</au><au>Dong, Haidong</au><au>Lohse, Christine M.</au><au>Park, Eugene S.</au><au>Kuntz, Susan M.</au><au>Leibovich, Bradley C.</au><au>Blute, Michael L.</au><au>Cheville, John C.</au><au>Kwon, Eugene D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>B7-H4 Expression in Renal Cell Carcinoma and Tumor Vasculature: Associations with Cancer Progression and Survival</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2006-07-05</date><risdate>2006</risdate><volume>103</volume><issue>27</issue><spage>10391</spage><epage>10396</epage><pages>10391-10396</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>16798883</pmid><doi>10.1073/pnas.0600937103</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Antigens, CD - metabolism B7-1 Antigen - metabolism B7-H1 Antigen Biological Sciences Cancer Carcinoma, Renal Cell - blood supply Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Carcinoma, Renal Cell - surgery Cardiovascular system Cells Disease Progression Female Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Immunotherapy Kidneys Male Middle Aged Nephrectomy Nephrology Pathology Renal cell carcinoma Specimens Survival Rate Survival rates T lymphocytes Treatment Outcome Tumors V-Set Domain-Containing T-Cell Activation Inhibitor 1 |
| title | B7-H4 Expression in Renal Cell Carcinoma and Tumor Vasculature: Associations with Cancer Progression and Survival |
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