B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration

Miyatake, Takashi; Tringler, Barbara; Liu, Wenhui; Liu, Shuhui; Papkoff, Jackie; Enomoto, Takayuki; Torkko, Kathleen C.; Dehn, Donna L.; Swisher, A.N.; Shroyer, Kenneth R.

doi:10.1016/j.ygyno.2007.03.039

Cited by 103 publications

(101 citation statements)

References 25 publications

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“…In the present study, the levels of B7-H4 were correlated with patient prognosis. Previous studies have detected B7-H4 expression in endometrial carcinoma (29,30). Although these studies also detected B7-H4 expression in normal endometrium, B7-H4 staining demonstrated that its expression increased from normal to malignant endometrial carcinoma, which is inconsistent with the results of the present study, in which B7-H4 was found to be highly expressed in both benign and malignant tissue.…”

Section: B Acontrasting

confidence: 99%

Expression of immune checkpoint molecules in endometrial carcinoma

Liu

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The main obstacle in the development of an effective tumor vaccine is the inherent ability of tumors to evade immune responses. Tumors often use common immune mechanisms and regulators to evade the immune system. The present study aimed to analyze the expression levels of indoleamine 2,3-dioxygenase (IDO), programmed death-ligand (PD-L) 1, PD-L2, B7-H4, galectin-1 and galectin-3 in tissue samples from patients with endometrial carcinoma, in order to detect the immunosuppressive environment of endometrial carcinomas. The levels of IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemical methods, and the levels of galectin-1 and galectin-3 in tumor lysates were determined using ELISA. PD-L2 was expressed at low levels in the majority of tumor samples. IDO expression was detected in 38, 63 and 43% of primary endometrial carcinoma, recurrent endometrial carcinoma, and metastatic endometrial carcinoma specimens, respectively. Positive expression rates for PD-L1 were 83% in primary endometrial carcinoma, 68% in recurrent endometrial carcinoma, and 100% in metastatic endometrial carcinoma, whereas B7-H4 expression was detected in 100% of both primary endometrial carcinoma and recurrent endometrial carcinoma samples, and in 96% of metastatic endometrial carcinoma specimens. The expression levels of galectin-1 and galectin-3 were not significantly different between the normal and tumor specimens. The results of the present study suggest that the interaction between PD-1/PD-L1 and B7-H4 may be a potential target for immune intervention in the treatment of endometrial carcinoma. Furthermore, the results may provide the basis for immunosuppressant therapy in the treatment of patients with uterine cancer.

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Section: B Acontrasting

confidence: 99%

Expression of immune checkpoint molecules in endometrial carcinoma

Liu

Wang

et al. 2015

Experimental and Therapeutic Medicine

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“…Several evidences have demonstrated that the B7-H4 molecule promotes cancer progression via regulating T cell mediated antitumor immunity (Zang et al, 2003;Sica et al, 2003;Sun et al, 2012). Previous studies have showed that the higher expression of B7-family inhibitory molecules by tumor cells is significantly correlated with densities of TILs in human malignancies, such as gastric cancer and esophageal squamous cell carcinoma ( Miyatake et al, 2007;Arigami et al, 2011;Chen et al, 2011;Zhang et al, 2013). We hypothesized that B7-H4 expression also involved in the thyroid cancer progression through regulating the T cell response.…”

Section: Discussionmentioning

confidence: 91%

“…Recently, B7-H4 has been reported to be highly expressed in human cancer cells, and their protein levels in tumors significantly correlate with patients' clinicopathological features and postoperative prognosis (Miyatake et al, 2007;Awadallah et al, 2008;Arigami et al, 2011;Abadi et al, 2013). However, no reports have investigated the clinical significance of B7-H4 expression in patients with thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

Zhu¹,

Chu²,

Yang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which play a central role in the regulation of antigen-specific T cell-mediated immune responses. B7-H4, also referred to as B7x or B7S1, is a ligand within the B7 family that has been implicated as a negative regulator of T cell-mediated immunity. Robust B7-H4 protein expression is primarily restricted to activated T cells, B cells, dendritic cells, and monocytes.

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“…In the context of malignancy, the precise physiologic and pathologic role of B7-H3 expression has yet to be fully elucidated. Transfection of B7-H3 into experimental tumor lines (P815 mastocytoma, Colon-26, and EL-4 lymphoma) has been reported to accelerate in vivo tumor rejection, supporting a net (22,25), uterus (26), and kidney (27). Krambeck et al (27) recently evaluated B7x in 259 patients with renal cell carcinoma, demonstrating that tumor expression of B7x was associated with adverse pathologic features (including advanced tumor size, grade, and stage) and an increased risk of death from disease (27).…”

Section: Discussionmentioning

confidence: 93%

“…Despite mRNA expression in various human tissues, immunohistochemistry (IHC) for B7x fails to reveal detectable protein expression in any healthy human organs (23). In stark contrast, aberrant expression of B7x has been observed in cancers of the breast (22,24), lung (16), ovary (22,25), uterus (26), and kidney (27). Thus, B7x, and perhaps B7-H3, have been proposed as potential therapeutic targets in human malignancy.…”

mentioning

confidence: 99%

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

Zang

Thompson²,

Al‐Ahmadie³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

350

327

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B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P ‫؍‬ 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P ‫؍‬ 0.005) and cancer-specific death (P ‫؍‬ 0.004 and P ‫؍‬ 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.immune tolerance ͉ prostatic neoplasms ͉ treatment outcome ͉ biological tumor markers

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B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration

Cited by 103 publications

References 25 publications

Expression of immune checkpoint molecules in endometrial carcinoma

Expression of immune checkpoint molecules in endometrial carcinoma

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

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