Clinical significance of the induction of macrophage differentiation by the costimulatory molecule B7-H3 in human non-small cell lung cancer

Abstract

B7-H3, a member of the B7 family of molecules, is expressed in certain types of human cancer and is important in tumor development and progression. Although several studies have reported that the expression of B7-H3 is correlated with poor outcomes in patients with cancer, its exact role in cancer remains unknown. In the present study, the expression levels of B7-H3 in the pathological specimens of 105 patients treated for non-small cell lung cancer (NSCLC) were examined by immunohistochemistry. A high expression level of B7-H3 was observed in 46.9% of the 105 NSCLC tissue specimens. These patients demonstrated a more advanced tumor grade and a shorter survival time. In addition, we also examined the levels of tumor-associated macrophages (TAMs) in NSCLC tissues and observed that the levels were positively correlated with the expression of B7-H3, and that higher levels of macrophages were associated with lower levels of infiltrating T cells and a shorter survival time. These results demonstrated that TAMs are important in the evasion of tumor immune surveillance in NSCLC. Furthermore, through knockdown of B7-H3 by RNA interference, we observed that soluble B7-H3 was capable of inducing macrophages to express higher levels of macrophage mannose receptor (MMR) and lower levels of human leukocyte antigen (HLA)-DR, as well as higher levels of interleukin-10 (IL-10) and lower levels of IL-1β in vitro. These observations are characteristic of an anti-inflammatory/reparatory (alternative/M2) phenotype. Therefore, our data suggests that B7-H3 proteins are involved in the progression of NSCLC by inducing the development of monocytes into anti-inflammatory cells.

ILT4 drives B7‐H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7‐H3 co‐expression correlates with poor prognosis in non‐small cell lung cancer

“…We first established that B7-H3 is expressed in NSCLC cells and correlates with a reduction in the number of TILs in tumour tissues [28]. Other groups have demonstrated that B7-H3 expression clearly inhibits T cell-mediated antitumour immunity in NSCLC [15,16]. Interestingly, we also previously demonstrated that ILT4 expression in NSCLC cells is negatively correlated with the number of TILs, indicating a potential role of ILT4 in the inhibition of T cell function in the tumour environment similar to that of B7-H3 [10].…”

Aberrant expression of B7-H3 in gastric adenocarcinoma promotes cancer cell metastasis

“…Zhang et al found that circulating B7-H3 in serum is a highly sensitive biomarker for non-small cell lung cancer (NSCLC), and increased circulating B7-H3 suggests a poor clinical prognosis for NSCLC (28). Sun et al reported that in the NSCLC environment the B7-H3 signaling pathway may be involved in switching macrophages to the M2 phenotype and the negative regula tion of the T lymphocyte-mediated immune response, thus they hypothesized that B7-H3 is important in NSCLC progression (29). Qin et al found that the specific expression of B7-H3 in tumors and tumor vasculature in clear cell renal cell carcinoma makes it a useful target and prominent biomarker for tumor-specific antiangiogenic therapies.…”

Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3

“…Recently, numerous studies have revealed that B7-H3 is abnormally up-regulated in a variety of cancers, whereas the B7-H4 protein is barely detected in the majority of normal human tissues [24,25]. In addition, overexpression of B7-H3 has been suggested to be positively correlated with tumor size, progression and prognosis [25].…”