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Article: B7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity

TitleB7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity
Authors
Issue Date2015
Citation
Cancer Immunology Research, 2015, v. 3, n. 2, p. 184-195 How to Cite?
Abstract© 2014 American Association for Cancer Research. The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking coinhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefore, it is critical to understand the role of different B7 family members since they maybe suitable therapeutic targets. B7-H4 is another member that inhibits T-cell function, and it is also upregulated on a variety of tumors and has been proposed to promote tumor growth. Here, we investigate the role of B7-H4 in tumor development and show that B7-H4 expression inhibits tumor growth in two mouse models. Furthermore, we show that B7-H4 expression is required for antitumor immune responses in a mouse model of mammary tumorigenesis. We found that the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ upregulates B7-H4 expression on mouse embryo fibroblasts and that the upregulation of B7-H4 on tumors is dependent on T cells. Notably, patients with breast cancer with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.
Persistent Identifierhttp://hdl.handle.net/10722/292899
ISSN
2023 Impact Factor: 8.1
2023 SCImago Journal Rankings: 3.781
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRahbar, Ramtin-
dc.contributor.authorLin, Albert-
dc.contributor.authorGhazarian, Magar-
dc.contributor.authorYau, Helen Loo-
dc.contributor.authorParamathas, Sangeetha-
dc.contributor.authorLang, Philipp A.-
dc.contributor.authorSchildknecht, Anita-
dc.contributor.authorElford, Alisha R.-
dc.contributor.authorGarcia-Batres, Carlos-
dc.contributor.authorMartin, Bernard-
dc.contributor.authorBerman, Hal K.-
dc.contributor.authorLeong, Wey L.-
dc.contributor.authorMcCready, David R.-
dc.contributor.authorReedijk, Michael-
dc.contributor.authorDone, Susan J.-
dc.contributor.authorMiller, Naomi-
dc.contributor.authorYoungson, Bruce-
dc.contributor.authorSuh, Woong Kyung-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorOhashi, Pamela S.-
dc.date.accessioned2020-11-17T14:57:27Z-
dc.date.available2020-11-17T14:57:27Z-
dc.date.issued2015-
dc.identifier.citationCancer Immunology Research, 2015, v. 3, n. 2, p. 184-195-
dc.identifier.issn2326-6066-
dc.identifier.urihttp://hdl.handle.net/10722/292899-
dc.description.abstract© 2014 American Association for Cancer Research. The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking coinhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefore, it is critical to understand the role of different B7 family members since they maybe suitable therapeutic targets. B7-H4 is another member that inhibits T-cell function, and it is also upregulated on a variety of tumors and has been proposed to promote tumor growth. Here, we investigate the role of B7-H4 in tumor development and show that B7-H4 expression inhibits tumor growth in two mouse models. Furthermore, we show that B7-H4 expression is required for antitumor immune responses in a mouse model of mammary tumorigenesis. We found that the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ upregulates B7-H4 expression on mouse embryo fibroblasts and that the upregulation of B7-H4 on tumors is dependent on T cells. Notably, patients with breast cancer with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.-
dc.languageeng-
dc.relation.ispartofCancer Immunology Research-
dc.titleB7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/2326-6066.CIR-14-0113-
dc.identifier.pmid25527357-
dc.identifier.scopuseid_2-s2.0-84939633426-
dc.identifier.volume3-
dc.identifier.issue2-
dc.identifier.spage184-
dc.identifier.epage195-
dc.identifier.eissn2326-6074-
dc.identifier.isiWOS:000349422600010-
dc.identifier.issnl2326-6066-

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