Expression of B7-H3 in hypopharyngeal squamous cell carcinoma as a predictive indicator for tumor metastasis and prognosis

Abstract

Abstract. B7-H3 is a member of the B7 family thought to be a co-regulatory factor of antigen-specific T-cell immune response via co-stimulatory and co-inhibitory receptors. We evaluated its potential expression in head and squamous cell carcinoma (Scc) cell lines, and in clinical tissue samples obtained from 37 patients with human hypopharyngeal Scc. all head and neck Scc cell lines tested expressed both the B7-H3 gene and cell surface protein. the staining intensity of immunoreactivity by tumor cells was blindly evaluated by two head and neck surgeons and the results were categorized into 4 grades according to staining intensity. eighty-seven percent of patients expressed B7-H3. B7-H3 expression was inversely correlated with the number of tumor infiltrating CD8 + t-cells (r=-0.4339, p=0.023). Patients who developed distant metastasis after tumor-free periods showed significantly higher B7-H3 expression scores compared to patients who did not develop distant metastasis during follow-up periods (p=0.048). Distant metastasis control ratio in patients with strong B7-H3 expression was significantly lower compared to that in patients with no to intermediate B7-H3 expression (p=0.040). causespecific survival ratio in patients with strong B7-H3 expression was significantly lower compared to that in patients with no to intermediate B7-H3 expression (p=0.028). Moreover, multivariate analysis revealed that strong B7-H3 expression was an independent prognostic factor in tumor-specific death in hypopharyngeal SCC (hazard ratio: 9.803, confidence interval: 0.018-0.539, p=0.0110). IntroductionHypopharyngeal Scc is one of the most aggressive head and neck tumor. Hypopharyngeal Scc tend to present with advanced primary disease, and nodal metastasis is highly likely. the most important features determining prognosis are the size and extent of local spread of the primary carcinoma and the extent of involvement of regional lymph nodes. Distant metastasis at presentation is more common in hypopharyngeal cancers than in other head and neck cancers (1). approximately 80% of hypopharyngeal cancer is stage iii or iV at presentation, with locally advanced disease present in the majority, and it has been estimated that 20% are inoperable at the time of diagnosis (2-4). owing to its extremely high malignant potential, it is usually diagnosed at an advanced stage and often recurs even after curative therapies. Despite recent improvements in diagnostic imaging, radiation and chemotherapy, and improved surgical techniques, there has not been significant impact on the survival of patients with hypopharyngeal SCC (1). Therefore, strenuous efforts to find novel cancer-related molecules for diagnosis and targeted therapeutic procedure will be required to predict and improve prognosis of the patients with hypopharyngeal Scc.one mechanism that has been reported for tumor-associated immune suppression in certain cancers is the aberrant expression of inhibitory t-cell co-regulatory molecules by tumor cells (5-15). Tumor infiltrating lymphocytes (TIL...

Prognostic significance of B7-H3 expression in patients with colorectal cancer: A meta-analysis

“…There is no doubt that the B7 family is an important cancer player, thus the B7-H3 study will be very promising in the field of malignancy research. High expression of B7-H3 strengthened the resistance to chemotherapeutics and anti-apoptotic ability, nevertheless knockdown of B7-H3 might enhance the sensitivity of apoptosis induced by drug 34-37. Up to now, many studies had reported that the high-expression of B7-H3 significantly correlated with lymphatic metastasis and lymphangiogenesis in CRC 18,22,23.…”

Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer

“…39 The expression of inhibitory ligands are up-regulated in many cancer types, 16,[40][41][42] and this is linked to poor patient prognosis. 43 However, the mechanistic consequences of this abnormal expression have not been fully defined previously.…”

Characterization of a Soluble B7-H3 (sB7-H3) Spliced from the Intron and Analysis of sB7-H3 in the Sera of Patients with Hepatocellular Carcinoma

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