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B7-H3 and B7-H4 expression in non-small-cell lung cancer
Yuping Sun1, Yunshan Wang, Jianqiang Zhao
1Immunological Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm S-17176, Sweden.
Abstract:
Inhibitory regulatory functions of B7-H3 and B7-H4 regarding T-cell activation have been reported recently. Little is known about the significance of human B7-H3 and B7-H4 expression in non-small-cell lung cancer (NSCLC), and we conducted the present study to address this issue in cell lines and tumor tissue from 70 patients. B7-H3 is over-expressed by all six NSCLC cell lines on both mRNA and protein level. B7-H4 is only transcripted by one cell line in which an alternatively spliced form was discovered. In tumor tissues, expression of B7-H3 and B7-H4 was found both on the cell membrane and in the cytoplasm. Thirty-seven percent of the specimens expressed B7-H3 and 43% B7-H4. The number of T infiltrating lymphoid cells (TILs) in the tumor tissues that expressed B7-H3 or B7-H4 was much lower than those who did not. There was a significant positive relation between the expression of B7-H3 and B7-H4, and high B7-H3 or B7-H4 expression was significantly more common in cases with lymph node metastasis. These observations suggest the contribution of B7-H3 and B7-H4 to immune dysfunction and tumor progression in NSCLC patients. B7-H3 and B7-H4 may be an important target for diagnosis and/or therapy of NSCLC.
Insights
B7-H3 and B7-H4 expression is common in non-small cell lung cancer (NSCLC), correlating with immune dysfunction and metastasis. These molecules may serve as diagnostic or therapeutic targets for NSCLC.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- B7-H3 and B7-H4 are known to inhibit T-cell activation.
- Their role in non-small cell lung cancer (NSCLC) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and significance of B7-H3 and B7-H4 in NSCLC cell lines and patient tumor tissues.
Main Methods:
- Analysis of B7-H3 and B7-H4 mRNA and protein expression in six NSCLC cell lines.
- Immunohistochemical analysis of B7-H3 and B7-H4 expression in tumor tissues from 70 NSCLC patients.
- Correlation analysis with tumor characteristics and tumor-infiltrating lymphocytes (TILs).
Main Results:
- B7-H3 was over-expressed in all NSCLC cell lines at both mRNA and protein levels.
- B7-H4 was transcribed in one cell line, with an alternatively spliced form identified.
- Expression of B7-H3 and B7-H4 was detected in the cell membrane and cytoplasm of tumor tissues.
- 37% of specimens expressed B7-H3 and 43% expressed B7-H4.
- Lower numbers of TILs expressed B7-H3 or B7-H4 compared to non-expressing TILs.
- Significant positive correlation between B7-H3 and B7-H4 expression.
- High expression of B7-H3 or B7-H4 was more frequent in cases with lymph node metastasis.
Conclusions:
- B7-H3 and B7-H4 expression in NSCLC is associated with immune dysfunction and tumor progression.
- These molecules may contribute to lymph node metastasis.
- B7-H3 and B7-H4 represent potential diagnostic and/or therapeutic targets for NSCLC.
