The New B7s: Playing a Pivotal Role in Tumor Immunity

Flies, Dallas B.; Chen, Lieping

doi:10.1097/cji.0b013e31802e085a

Cited by 179 publications

(139 citation statements)

References 118 publications

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“…The costimulatory B7 family members are cell-surface protein ligands, binding to receptors on lymphocytes to regulate immune responses (Flies et al, 2007). They not only provide positive signals to stimulate T-cell activation, but also regulate negative signals to inhibit T-cell responses.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that the activation of the B7-H4 signaling pathway may lead to tumor cells escaping from immune surveillance (Flies and Chen, 2007;Arigami et al, 2011;Sun et al, 2012). Recent report showed that host B7-H4 may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems (Abadi et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

Zhu¹,

Chu²,

Yang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which play a central role in the regulation of antigen-specific T cell-mediated immune responses. B7-H4, also referred to as B7x or B7S1, is a ligand within the B7 family that has been implicated as a negative regulator of T cell-mediated immunity. Robust B7-H4 protein expression is primarily restricted to activated T cells, B cells, dendritic cells, and monocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

Zhu¹,

Chu²,

Yang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…12 PD-1 expression has also been identified on a small fraction of melanoma cells, where its ligation promotes tumor growth. 13 The known ligands for PD-1 are the B7 family molecules PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273), [14][15][16][17][18][19][20] which are cell membrane-bound glycoproteins that share 40% amino acid homology to each other. In normal human tissues, PD-L1 is expressed by myeloid dendritic cells (DC), macrophages, placental trophoblasts, myocardial endothelium and cortical thymic epithelial cells, 21,22 whereas PD-L2 is expressed by DC, macrophages, placental endothelium and medullary thymic epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

et al. 2016

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Therapeutic blockade of PD-1/PD-L1 can have dramatic therapeutic benefit in some patients; however, the prognostic associations of PD-1 and its ligands, in the absence of therapeutic blockade have not been definitively addressed. In particular, associations of PD-L2 with immune infiltrates and with outcome have yet to be explored. We hypothesized that surface expression of both PD-L1 and PD-L2 by melanoma cells would be associated with immune cell infiltration and with overall patient survival, independent of checkpoint blockade therapy. We also characterized the heterogeneity of their distribution within a tumor and within tumors of the same patient. Tissue microarrays of metastatic melanoma samples from 147 patients were quantified for CD8 C , CD45, CD4 C , CD3, CD163, CD20, CD138, FoxP3, PD-1, PD-L1 and PD-L2 markers by immunohistochemistry. Relationships between the proportions of PD-L1 and PD-L2 expressing tumor cells with the immune cell count, distribution (immunotype) and patient survival were studied. Expressions of both PD-L1 and PD-L2 correlated significantly with increasing densities of immune cells in the tumor specimens and with immunotype. Positive PD-L2 expression was associated with improved overall survival and the simultaneous positive expression of both PD-1 ligands showed a higher association with survival. Significant heterogeneity of PD-L1 and PD-L2 expressions within tumors were observed, however, they were less pronounced with PD-L2. In conclusion, both are markers of immune infiltration and PD-L2, alone or in combination with PD-L1, is a marker for prognosis in metastatic melanoma patients. Larger tumor samples yield more reliable assessments of PD-L1/L2 expression.

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“…Whereas HLA-B-associated transcript 3 has been reported to be expressed by both malignant and healthy cells such as dendritic cells (16,18), B7-H6 to date has not been found on normal cells, suggesting that this ligand may be exclusively displayed by aberrant cells and to be absent from healthy tissues (15,21). The ligand B7-H6 belongs to the B7 molecule family comprising several members that exert both immune stimulatory and inhibitory functions (22). The tumor-restricted expression pattern, binding specificity for the stimulatory NKp30 receptor, and its ability to trigger NK cell cytotoxicity suggest that B7-H6 may play a pivotal role as an "induced self" alert signal for NK cells.…”

mentioning

confidence: 99%

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

Kellner

Maurer

Hallack

et al. 2012

The Journal of Immunology

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Induced self expression of the NKp30 ligand B7-H6 facilitates NK cell-mediated elimination of stressed cells. A fusion protein consisting of the ectodomain of B7-H6 and the CD20 single-chain fragment variable 7D8 was generated to mimic an induced self phenotype required for NK cell-mediated target cell elimination. B7-H6:7D8 had bifunctional properties as reflected by its ability to simultaneously bind to the CD20 Ag and to the NKp30 receptor. B7-H6:7D8 bound by CD20+ lymphoma cells activated human NK cells and triggered degranulation. Consequently, the immunoligand B7-H6:7D8 induced killing of lymphoma-derived cell lines as well as fresh tumor cells from chronic lymphocytic leukemia or lymphoma patients. B7-H6:7D8 was active at nanomolar concentrations in a strictly Ag-specific manner and required interaction with both CD20 and NKp30. Remarkably, NK cell cytotoxicity was further augmented by concomitant activation of Fcγ receptor IIIa or NK group 2 member D. Thus, B7-H6:7D8 acted synergistically with the CD20 Ab rituximab and the immunoligand ULBP2:7D8, which was similarly designed as B7-H6:7D8 but engaging the NK group 2 member D receptor. In conclusion, to our knowledge, B7-H6:7D8 represents the first Ab-based molecule stimulating NKp30-mediated NK cell cytotoxicity for therapeutic purposes and provides proof of concept that Ag-specific NKp30 engagement may represent an innovative strategy to enhance antitumoral NK cell cytotoxicity.

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The New B7s: Playing a Pivotal Role in Tumor Immunity

Cited by 179 publications

References 118 publications

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

B7-H4 Expression is Associated with Cancer Progression and Predicts Patient Survival in Human Thyroid Cancer

PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

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