B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma
Ilona Kryczek,Ilona Kryczek,Linhua Zou,Linhua Zou,Paulo C. Rodriguez,Gefeng Zhu,Shuang Wei,Shuang Wei,Peter Mottram,Michael J. Brumlik,Pui Cheng,Tyler J. Curiel,Leann Myers,Andrew A. Lackner,Xavier Alvarez,Augusto C. Ochoa,Lieping Chen,Weiping Zou,Weiping Zou +18 more
TL;DR: B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer and represent a critical checkpoint in determining host responses to dysfunctional cytokines in ovariancancer.
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Abstract: Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.
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Citations
Data from B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response
31 Mar 2023
TL;DR: In this article , B7H3 and B7-H4 expression was detected in primary tumor lesions (29 of 29 and 28 of 29) and in metastases (28 of 28 and 26 of 29), and the survival curves and log-rank tests were used to test the association of protein expression with survival.
Tumorsexpressantigensthatshouldinduceimmune-mediatedrejection,butspontaneousrejectionofestab- lishedtumorsisrare.Recentworkdemonstratesthatonereasonforthelackoftumorrejectionisthattumors activelydefeathostimmunity.Thisconceptforcesustorethinkcurrentapproachestoharnessingpotent,spe- cifichostimmunitytobattlecancer,mostofwhicharebasedontheparadigmthatinducingmoreantitumor immunecellsaloneistherapeutic.However,asIdiscussinthisPersonalPerspective,anewerparadigmpredicts thatreducingtumor-drivenimmunesuppressionwillbeclinicallybeneficial.CD4 + CD25 + Tregsareonemecha- nismoftumor-drivenimmuneevasionthatprovideprototypicaltargetsfortestingnovelanticancertreatment
Tyler J. Curiel
- 01 Jan 2007
Analogies immunologiques du cancer de l’ovaire et de la grossesse
TL;DR: Journal de Gynecologie Obstetrique et Biologie de the Reproduction - Vol.
Patent
Anticorps anti-b7-h4 et leurs utilisations
Linda Liu,Shannon Marshall,Solomon Langermann +2 more
- 15 Aug 2012
TL;DR: In this article, an invention concerne des anticorps and their fragments de liaison a un antigene et d'autres molecules (comprenant des proteines de fusion qui se lient a l'antigene/au recepteur cognate, etc.) who sont aptes a se lier de facon immunospecifique a B7-H4, and les utilisations de telles molecules dans le diagnostic et le traitement du cancer et d-autres maladies.
Data from Myeloid Cells Obtained from the Blood but Not from the Tumor Can Suppress T-cell Proliferation in Patients with Melanoma
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TL;DR: In this paper , the frequency, phenotype, and suppressive function of myeloid-derived suppressor cells (MDSC) in patients with melanoma were investigated. And the authors found no differences in the frequency and phenotype of MDSC-derived subsets in the blood of patients suffering from melanoma compared with healthy donors.
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