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B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma

Abstract

Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan–Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC.

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Abbreviations

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

ESCC:

Esophageal squamous cell carcinoma

MDSCs:

Myeloid-derived suppressor cells

OSCC:

Oral squamous cell carcinoma

PD-1:

Programmed death-1

PD-L1:

Programmed death-ligand 1

RCC:

Renal cell carcinoma

TPF:

Cisplatin, docetaxel, and fluorouracil

Tregs:

Regulatory T cells

WT:

Wild type

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Acknowledgments

This work was supported by National Natural Science Foundation of China 81272963, 81472528 (Zhi-Jun Sun), 81272964, 81472529 (Wen-Feng Zhang). Zhi-Jun Sun was supported by program for new century excellent talents in university (NCET-13-0439), Ministry of Education of China.

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Correspondence to Zhi-Jun Sun.

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Lei Wu and Wei-Wei Deng have contributed equally to this work.

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Wu, L., Deng, WW., Yu, GT. et al. B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma. Cancer Immunol Immunother 65, 1035–1045 (2016). https://doi.org/10.1007/s00262-016-1867-9

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  • DOI: https://doi.org/10.1007/s00262-016-1867-9

Keywords

  • B7-H4
  • Immune checkpoint
  • Immunotherapy
  • Oral squamous cell carcinoma
  • Transgenic mice
  • Tissue microarray