Negative roles of B7-H3 and B7-H4 in the microenvironment of cervical cancer

Han, Sai; Wang, Ying; Shi, Xuejiao; Zong, Liju; Liu, Lu; Zhang, Juan; Qian, Qiuhong; Jin, Jing; Ma, Yana; Cui, Baoxia; Yang, Xingsheng; Kong, Beihua; Zhang, Youzhong

doi:10.1016/j.yexcr.2018.08.014

Cited by 37 publications

(31 citation statements)

References 37 publications

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“…Abbreviations: LSIL: low-grade squamous intraepithelial lesion; HSIL: high-grade squamous intraepithelial lesion; SCC: squamous cervical carcinoma; UCAC: uterine cervical adenocarcinoma. ****p < 0.0005, ***p = 0.001, *p < 0.05 microenvironment of cervical cancer, until now, there have been no reports examining B7-H6 expression in cervical intraepithelial lesions or cervical cancer [26][27][28]. The findings of our present study demonstrate for the first time that B7-H6 is not expressed in the abnormal epithelial cells of low-grade squamous intraepithelial lesions (LSIL); while, in contrast, when the stage of the lesion is more advanced, such as high-grade squamous intraepithelial lesion (HSIL) or both cancer types, squamous cervical carcinoma (SCC) or uterine cervical adenocarcinoma (UCAC), there is a positive correlation with the immunoreactive score (IRS) for immunohistochemical B7-H6 detection.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Accumulating evidence indicated that B7-H3 participates in the metastasis and stemness regulation in some tumor cells. [27][28][29] B7-H3 could facilitate the cancer migration and invasion through the activation of AKT/STAT3 signals in bladder cells. Also, the expression of B7-H3 has been proved to be associated with the sustained cancer cells proliferation and poor prognosis of brain cancer and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>B7-H3 Induces Ovarian Cancer Drugs Resistance Through An PI3K/AKT/BCL-2 Signaling Pathway</p>

Zhou¹,

Zhao²

2019

CMAR

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Purpose: This study was aimed to investigate the underlying mechanism of B7-H3 induced ovarian cancer proliferation and drugs resistance. Materials and methods: We compared the expression of B7-H3 in ovarian tumor tissues from high-malignant or low-malignant patients by immunohistochemistry. We established B7-H3 overexpression and knockout ovarian cells by CRISPR-Cas9 technology and examined the expression of the PI3K/AKT/BCL-2 signals in tumor cells by Western blot or immunofluorescence. We detected the B7-H3 overexpression ovarian cancer cells drugs resistance by CCK8 cell proliferation analysis and Annexin V/PI staining. Tumor-bearing mice were used to investigate the anticancer effects of PI3K/AKT inhibitors in combination with B7-H3 neutralizing antibodies. Results: Enhanced expression of B7-H3 was observed in ovarian tumor tissues from highmalignant patients compared to those from low-malignant patients. Notably, B7-H3 overexpression caused enhanced cells proliferation and chemo-resistance in vitro and in vivo through the activation of PI3K/AKT signaling pathways and up-regulation of BCL-2 protein.Combination of chemotherapeutic agents and B7-H3 neutralizing antibodies efficiently reverses the drugs resistance induced by B7-H3, resulting in improved anticancer effects in ovarian cancer. Conclusion: B7-H3 expression induces the activation the PI3K/AKT signaling pathway and up-regulates BCL-2 in protein level, resulting in the sustained growth and chemo-resistance in ovarian cancer. Blockade of B7-H3 signals efficiently reverses the chemo-resistance, which provides an innovative target in ovarian cancer treatment.

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“…The PD-1 inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical cancer expressing PD-L1. While the expression and clinical significance of the immune checkpoints PD-L1, B7-H3, and B7-H4 have been reported in common types of cervical cancer [8][9][10][11], the immune microenvironment and expression status of immune checkpoints in CCC of the cervix remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

Zong

Zhang

Zhou

et al. 2020

Journal of Immunology Research

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The purpose of this study was to investigate the expression levels of the immune checkpoint proteins, programmed cell death-ligand 1 (PD-L1), B7-H3, B7-H4, and V-domain Ig suppressor of T cell activation (VISTA), as well as the significance thereof, in clear cell carcinoma (CCC) of the cervix (a rare histological subtype of cervical cancer). We also compared the expression statuses of these biomarkers in cervical CCCs with those in cervical squamous cell carcinomas (SCCs). We evaluated the expression of PD-L1, B7-H3, B7-H4, and VISTA in 50 cervical CCCs and 100 SCCs using immunohistochemical staining and investigated the associations between these markers, clinicopathologic features, and survival in patients with CCCs. Of the cervical CCC samples examined, 22%, 16%, 32%, and 34% were positive for PD-L1, B7-H3, B7-H4, and VISTA, respectively. Nineteen samples (38%) were negative for all 4 of these markers, whereas 31 (62%) expressed at least 1 marker. None of these markers was associated with the investigated clinicopathologic variables or patient survival. PD-L1, B7-H3, and VISTA were observed significantly more frequently in SCCs than in CCCs of the cervix. Our study confirmed the expression of immune checkpoint proteins in cervical CCCs and indicated their nonredundant and complementary roles. As such, our data suggest that monotherapeutic immune checkpoint blockade may not be sufficiently effective in patients with cervical CCC.

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Negative roles of B7-H3 and B7-H4 in the microenvironment of cervical cancer

Cited by 37 publications

References 37 publications

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

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

<p>B7-H3 Induces Ovarian Cancer Drugs Resistance Through An PI3K/AKT/BCL-2 Signaling Pathway</p>

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

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