Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

Abstract

Background: B7-H6 has been revealed as an endogenous immunoligand expressed in a variety of tumors, but not expressed in healthy tissues. Heretofore, no studies have been reported describing B7-H6 in women with cervical cancer. To investigate this question, our present study was conducted. Results: This retrospective study comprised a total of 62 paraffinized cervical biopsies, which were distributed in five groups: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cervical carcinoma (SCC), uterine cervical adenocarcinoma (UCAC), and a group of cervicitis (as a control for non-abnormal/non-transformed cells). Cervical sections were stained by immunohistochemistry to explore the expression of B7-H6, which was reported according to the immunoreactive score (IRS) system. We observed a complete lack of B7-H6 in LSIL abnormal epithelial cells. Interestingly, B7-H6 began to be seen in HSIL abnormal epithelial cells; more than half of this group had B7-H6 positive cells, with staining characterized by a cytoplasmic and membranous pattern. B7-H6 in the SCC group was also seen in the majority of the sections, showing the same cytoplasmic and membranous pattern. Strong evidence of B7-H6 was notably found in UCAC tumor columnar cells (in 100% of the specimens, also with cytoplasmic and membranous pattern). Moreover, consistent B7-H6 staining was observed in infiltrating plasma cells in all groups. Conclusions: B7-H6 IRS positively correlated with disease stage in the development of cervical cancer; additionally, B7-H6 scores were found to be even higher in the more aggressive uterine cervical adenocarcinoma, suggesting a possible future therapeutic target for this cancer type.

B7-H6, an immunoligand for the natural killer cell activating receptor NKp30, reveals inhibitory effects on cell proliferation and migration, but not apoptosis, in cervical cancer derived-cell lines

“…We showed that the surface expression of B7-H6 was present in around 50% of the cells in both cervical cancer cell lines, HeLa and SiHa. We are among the first to show the presence of B7-H6 in these cell lines, and these results are in line with a recent report by our group, where the expression of B7-H6 was consistently seen in cervical cancer specimens [ 20 ] As the expression of B7-H6 was not present in the totality of HeLa or SiHa cells, we tried to sort the B7-H6 positive and B7-H6 negative population and found that B7-H6 was selectively maintained or lost in the tumor cell lines. Both the positive and negative cell lines regained the expression with roughly the same percentage.…”

“…The canonical role described for the B7-H6/NKp30 interaction is activation of the NK cell [ 16 , 17 ]. At a protein level, it has been found that B7-H6 is selectively expressed by a variety of malignant tumors, such as lymphoma, leukemia [ 10 ], gastric carcinoma [ 18 ], astrocytoma [ 19 ], cervical carcinoma [ 20 ] and is also expressed under inflammatory and stress conditions, but has not been seen in healthy cells [ 14 , 21 ]. Also, high amounts of B7-H6 mRNA have been found in ovarian cancer, brain tumors, breast cancer, and various sarcomas, while normal tissues under steady-state conditions apparently do not show detectable B7-H6 mRNA [ 22 ].…”

Dual role of B7‐H6 as a novel prognostic marker in hepatocellular carcinoma

“…Among these signals, B7‐H6 /NKp30 pathway is involved in the NK cell‐mediated immune responses and tumor progression within a variety of tumors. Several previous studies demonstrated that the high expression of B7‐H6 was correlated with tumor progression and poor overall survival in some cancers (19–24, 27–29). Different research groups showed that B7‐H6 has no significant diagnostic or prognostic value in non‐small cell lung cancer and gastric cancer (26, 27).…”

“…B7‐H6 was also expressed in inflammatory monocytes, but not in healthy monocytes (18). Studies have reported that the expression of B7‐H6 is related to the metastasis of some cancers, and the B7‐H6 expression is negatively correlated with the overall survival (OS) rate of ovarian cancer, breast cancer, brain tumor, esophageal squamous cell carcinoma, cervical cancer, and esophageal squamous cell carcinoma (17, 19–24). However, the situation is not always the same, and it was found that the higher expression of B7‐H6 predicted favorable overall patient survival in gastric cancer (25).…”

<p>Emerging Targets of Immunotherapy in Gynecologic Cancer</p>

“…95 It has been reported that the expression of B7-H6 is positively correlated with disease stage in the development of cervical cancer, and the expression level is higher in cervical adenocarcinoma than that in SCC. 96 The studies on B7-H6 in gynecologic tumors are all in the preclinical stage, and there is no relevant clinical trial ongoing at present.…”