B7‐H3 and Its Role in Antitumor Immunity

Loos, Martin; Hedderich, Dennis M.; Friess, Helmut; Kleeff, Jörg

doi:10.1155/2010/683875

Cited by 103 publications

(105 citation statements)

References 71 publications

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“…Increased TAM infiltration has been demonstrated to be associated with poorer prognosis in breast and ovarian cancer (30,31). The present results identified in patients with CRC were consistent with those of previous studies (10,24), and identified that the macrophages that infiltrate CRC tissues may have a harmful role in tumor immune response. The association between B7-H3 expression and expression of CD8 + T cells and CD68 + macrophages was then investigated.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, key factors that regulate tumor progression and antitumor immunity are required in the individualized therapy of human CRC. A previous study has demonstrated the clinical significance and regulation of B7-H3 expression in CRC patients (10). In the present study, we investigated the immune cells that infiltrated in CRC, and revealed the mechanism of B7-H3 signaling in the regulation of immune cells in the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 77%

“…The contrasting results revealed that there may be two or more receptors for B7-H3 with opposing functions, which remain unknown (9). The mechanism of B7-H3 in the tumor microenvironment remains unclear, and the regulation of T cell activation, resistance of drug-induced apoptosis and enhancement of metastasis were all considered as probable mechanisms (10). However, the exact role of B7-H3 in the tumor microenvironment remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

et al. 2017

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Abstract. Co-stimulatory molecule B7 homolog 3 protein (B7-H3) has been described as an important tumor antigen in various human tumors. The exact role of B7-H3 in tumor progression and its receptor are still ambiguous. The phenotype and the function of tumor-associated macrophages (TAMs) in human solid tumors are complicated and could contribute to the shaping of the tumor microenvironment. In the present study, B7-H3 expression and lymphocyte infiltration were investigated by immunohistochemistry in 117 colorectal carcinoma (CRC) patients. B7-H3 expression was positively associated with the infiltrating density of macrophage in CRC tissues, and B7-H3 expression and the infiltrating density of macrophages were negatively associated with the overall survival rate of patients. The putative B7-H3 receptor was found on activated monocytes and macrophages, indicating the direct function of B7-H3 signal on macrophages. Additional results revealed that during the differentiation of TAMs, B7-H3 promoted the polarization of type 2 macrophages (M2s) and switch of the M1 phenotype to the M2 phenotype. Thus, B7-H3 signaling promotes M2 differentiation via the putative receptor on monocytes and macrophages. Targeting the manipulation of TAMs through the B7-H3 pathway may be valuable for the development of novel immunotherapeutic strategies against human CRC.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

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Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

et al. 2017

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“…B7-H3 protein was also found on various cell types and organs. This broad expression pattern suggests more diverse immunological and probably nonimmunological functions of B7-H3, especially in peripheral tissues (18). Recently, B7-H3 has been Significance Oral squamous cell carcinoma (OSCC) is characterized by high morbidity and mortality, and few therapeutic options.…”

mentioning

confidence: 99%

Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response

Chen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

108

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The incidence and mortality rate of oral cancer continue to rise, partly due to the lack of effective early diagnosis and increasing environmental exposure to cancer-causing agents. To identify new markers for oral cancer, we used a sialylation probe to investigate the glycoproteins differentially expressed on oral cancer cells. Of the glycoproteins identified, B7 Homolog 3 (B7-H3) was significantly overexpressed in oral squamous cell carcinoma (OSCC), and its overexpression correlated with larger tumor size, advanced clinical stage, and low survival rate in OSCC patients. In addition, knockdown of B7-H3 suppressed tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor growth. It was also found that the N-glycans of B7-H3 from Ca9-22 oral cancer cells contain the terminal α-galactose and are more diverse with higher fucosylation and better interaction with DC-SIGN [DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin] and Langerin on immune cells than that from normal cells, suggesting that the glycans on B7-H3 may also play an important role in the disease.CD276 | proliferation | glycan sequencing | terminal α-galactose | fucose

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“…For example, B7-H3 is a member of a family of molecules known to inhibit immune TCR, T-cell receptor [7] reactions and to be upregulated in conditions promoting tumor growth [67]. Upregulation of this molecule in dendritic cells (as observed in NSCLC tumor samples) has been associated with impaired capacity to stimulate T-cell proliferation [68], although recently published data contradicts this finding in murine cancers and other human cancers [69]. Following these observations, strategies to encourage the immune system to recognize tumor antigens and shift the balance away from immune tolerance of tumors are being investigated for NSCLC.…”

Section: Modulation Of Dendritic Cell Phenotype With Recombinant Humamentioning

confidence: 99%

Targeting the immune system for management of NSCLC: the revival?

Reck

Vansteenkiste

Brahmer

2013

Curr Respir Care Rep

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Immunotherapy, based on increasing knowledge of the mechanisms of immune-mediated elimination of tumor cells, is a new approach to lung cancer therapy. This paper reviews clinical experience of two types of immunotherapy for lung cancer. In the first approach antigen-independent immunomodulatory therapy is used to target crucial immune checkpoints. This strategy includes use of ipilimumab-to block the interaction of cytotoxic T-lymphocyte antigen-4 with CD80 and/or CD86, thereby enhancing T-cell proliferation-and the fully human monoclonal antibodies BMS-936558 and BMS-936559-to target the programmed cell death protein 1 signaling pathway, thereby enhancing T-cell proliferation, cytokine secretion, and cytolysis of target cells. The second approach is antigen-specific cancer immunotherapy, including vaccines against melanoma-associated antigen 3, mucinous glycoprotein-1, transforming growth factor-beta 2, epidermal growth factor, and, less specifically, whole-tumor cell extracts. An overview of the clinical data from these strategies is presented, with discussion of questions and issues that remain unanswered.

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B7‐H3 and Its Role in Antitumor Immunity

Cited by 103 publications

References 71 publications

Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

Cancer cell‑expressed B7‑H3 regulates the differentiation of tumor‑associated macrophages in human colorectal carcinoma

Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response

Targeting the immune system for management of NSCLC: the revival?

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