Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma
- PMID: 17875732
- DOI: 10.1158/0008-5472.CAN-07-1866
Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma
Abstract
B7-H4 is a recently identified B7 family member. We previously showed that ovarian tumor and associated macrophages expressed B7-H4; tumor B7-H4+ macrophages and CD4+CD25+FOXP3+ regulatory T cells (Treg cells) suppressed tumor-associated antigen-specific T-cell immunity. To determine the pathologic relationship between B7-H4, macrophages, and Treg cells in the tumor environment, in addition to Treg cell numbers, we quantified B7-H4 expression in the tumor and tumor-associated macrophages in 103 patients with ovarian carcinoma. We observed that the intensity of B7-H4 expression in macrophages was significantly correlated with Treg cell numbers in the tumor. Further, both Treg cells and macrophage B7-H4, but not tumor B7-H4, were negatively associated with patient outcome. Tumor Treg cells enabled macrophages to spontaneously produce interleukin (IL)-10 and IL-6. Tumor macrophages stimulated B7-H4 expression in an autocrine manner through IL-10 and IL-6. Our previous work showed that tumor-associated macrophages spontaneously produced chemokine CCL22 to mediate Treg cell trafficking into tumor, and Treg cells induced B7-H4 on antigen-presenting cells (APC) including macrophages. Altogether, our data support the concept that there is a mechanistic interaction between Treg cells and macrophage, and that Treg cells may convey the suppressive activity to APCs through B7-H4 induction in human ovarian cancer.
Similar articles
-
B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration.Gynecol Oncol. 2007 Jul;106(1):119-27. doi: 10.1016/j.ygyno.2007.03.039. Epub 2007 May 16. Gynecol Oncol. 2007. PMID: 17509674
-
Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma.Cancer Res. 2007 Aug 1;67(15):7487-94. doi: 10.1158/0008-5472.CAN-07-0565. Cancer Res. 2007. PMID: 17671219 Clinical Trial.
-
Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells into proinflammatory interleukin 17-producing helper T cells.J Immunother. 2009 Feb-Mar;32(2):101-8. doi: 10.1097/CJI.0b013e318195b59e. J Immunother. 2009. PMID: 19238008
-
Regulatory T cells in ovarian cancer: biology and therapeutic potential.Am J Reprod Immunol. 2005 Dec;54(6):369-77. doi: 10.1111/j.1600-0897.2005.00330.x. Am J Reprod Immunol. 2005. PMID: 16305662 Review.
-
The significance of Treg cells in defective tumor immunity.Arch Immunol Ther Exp (Warsz). 2008 May-Jun;56(3):181-91. doi: 10.1007/s00005-008-0018-1. Epub 2008 May 30. Arch Immunol Ther Exp (Warsz). 2008. PMID: 18512029 Review.
Cited by
-
Prognostic value of soluble H7-B4 in pleural effusion associated with lung cancer.Tumour Biol. 2015 Jun;36(6):4397-403. doi: 10.1007/s13277-015-3079-x. Epub 2015 Feb 1. Tumour Biol. 2015. PMID: 25636447
-
Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer.Comput Math Methods Med. 2020 Sep 30;2020:6138039. doi: 10.1155/2020/6138039. eCollection 2020. Comput Math Methods Med. 2020. PMID: 33062039 Free PMC article.
-
The expression, function, and clinical relevance of B7 family members in cancer.Cancer Immunol Immunother. 2012 Aug;61(8):1327-41. doi: 10.1007/s00262-012-1293-6. Epub 2012 Jun 14. Cancer Immunol Immunother. 2012. PMID: 22695874 Free PMC article. Review.
-
Cancer immunotherapy: the role regulatory T cells play and what can be done to overcome their inhibitory effects.Curr Mol Med. 2009 Aug;9(6):673-82. doi: 10.2174/156652409788970670. Curr Mol Med. 2009. PMID: 19689294 Free PMC article. Review.
-
Chimeric NKG2D expressing T cells eliminate immunosuppression and activate immunity within the ovarian tumor microenvironment.J Immunol. 2009 Dec 1;183(11):6939-47. doi: 10.4049/jimmunol.0902000. Epub 2009 Nov 13. J Immunol. 2009. PMID: 19915047 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous