B7.1 on Human Carcinomas: Costimulation of T Cells and Enhanced Tumor-Induced T-Cell Death

Lang, Stephan; Atarashi, Yoshinari; Nishioka, Yasushiko; Stanson, Joanna; Meidenbauer, Norbert; Whiteside, Theresa L.

doi:10.1006/cimm.2000.1651

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…PCI cells denoted "A" and "B" were derived from autologous primary and metastatic tumors, respectively. The CD80 (B7.1) transfected PCI-13 cell line, a gift from Dr. T. L. Whiteside (University of Pittsburgh Cancer Institute), has been previously described (16). Both the melanoma cell line MEL-526 and the breast carcinoma cell line MCF-7 have been described and characterized elsewhere (17,18).…”

Section: Cell Linesmentioning

confidence: 99%

Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL

López-Albaitero¹,

Nayak²,

Ogino

et al. 2006

The Journal of Immunology

148

137

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Squamous cell carcinoma of the head and neck (SCCHN) cells are poorly recognized in vitro by CTL despite expressing the restricting HLA class I allele and the targeted tumor Ag (TA). Several lines of evidence indicate that the lack of SCCHN cell recognition by CTL reflects defects in targeted TA peptide presentation by HLA class I Ag to CTL because of Ag-processing machinery (APM) dysfunction. First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-γ-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin. Second, SCCHN cell recognition by CTL is restored by pulsing cells with exogenous targeted TA peptide. Third, the restoration of CTL recognition following incubation of SCCHN cells with IFN-γ is associated with a significant (p = 0.001) up-regulation of the APM components TAP1, TAP2, and tapasin. Lastly, and most conclusively, SCCHN cell recognition by CTL is restored by transfection with wild-type TAP1 cDNA. Our findings may explain the association between APM component down-regulation and poor clinical course of the disease in SCCHN. Furthermore, the regulatory nature of the APM defects in SCCHN cells suggests that intralesional administration of IFN-γ may have a beneficial effect on the clinical course of the disease and on T cell-based immunotherapy of SCCHN by restoring SCCHN cell recognition by CTL.

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Section: Cell Linesmentioning

confidence: 99%

Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL

López-Albaitero¹,

Nayak²,

Ogino

et al. 2006

The Journal of Immunology

148

137

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“…Antigen presentation by keratinocytes is believed to have a role in OLP pathogenesis, and data on CD86 expression are inconsistent (1,(17)(18)(19)(20)(21)(22)(23)(24). Thus, we investigated CD86 mRNA expression in oral epithelial cells because of its crucial role in this process.…”

Section: Introductionmentioning

confidence: 99%

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

et al. 2017

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Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP. In the present study, we used a reverse transcriptase-polymerase chain reaction assay to assess whether CD40-a receptor found mainly on antigen presenting cells-and the costimulatory molecule CD86 were expressed in oral keratinocytes (three strains of primary normal oral keratinocytes and the H357 cell line) in the presence or absence of IFN-γ. To further characterize the involvement of CD40 in OLP, expression and distribution of receptor and ligand (CD40/CD154) in tissues from OLP were evaluated by immunohistochemistry. The present results are the first to show that both CD40 and CD86 are constitutively expressed at low levels in oral keratinocytes and that their expression was enhanced by IFN-γ stimulation. The intensity of CD40 staining in OLP tissues was strong. Taken together, the results strongly suggest that CD40 and CD86 play a role in the pathophysiology of oral inflammatory diseases such as OLP.

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“…Although it is possible to generate ex vivo antitumor T cell responses with tumor cells genetically modified to express naturally occurring CD80 or in combination with other costimulatory molecules as stimulators, several rounds of ex vivo stimulation are necessary for a detectable response (Lang et al, 2000;Schendel et al, 2000;Mazzocchi et al, 2001). The strong immunostimulatory effects of CD80-SA observed in this study may be attributed to the high levels of this molecule on the surface of decorated tumor cells (100,000 to 125,000 molecules per cell; K.G.…”

Section: Discussionmentioning

confidence: 99%

Primary Tumor Cells Resected from Cancer Patients and Decorated with a Novel Form of CD80 Protein Serve as Effective Antigen-Presenting Cells for the Induction of Autologous T Cell Immune Responses Ex Vivo

Singh

Miller²,

Yolcu³

et al. 2006

Human Gene Therapy

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Vaccination with autologous tumor cells genetically modified to express costimulatory molecules has shown utility for cancer immunotherapy in preclinical and limited clinical settings. Given the complicated nature of gene therapy, a practical alternative approach has been designed that relies on modification of the cell membrane with biotin and its "decoration" with a chimeric protein composed of the functional portion of human CD80 and core streptavidin (CD80-SA). We tested whether primary tumor cells resected from cancer patients can be decorated with CD80-SA and whether such cells serve as antigen-presenting cells (APCs) to generate autologous T cell responses ex vivo. Tumors and peripheral blood lymphocytes (PBLs) were collected from 14 lung, 9 colon, and 2 breast "treatment-naive" cancer patients presenting various clinical stages of the disease. Tumors were mechanically processed, irradiated, decorated with CD80-SA or control streptavidin (SA) protein, and used as APCs in ex vivo autologous T cell-proliferative and cytotoxicity assays. All tumor samples were modified with CD80-SA, albeit with various degrees of decoration ranging from 21.8 to 100%. CD80- SA-decorated cells generated significant proliferative responses in autologous T cells from 9 of 16 evaluable patients (p < 0.05). Proliferative responses were CD80-SA specific and heterogeneous, with stimulation indices ranging from 0.25 to 45. In 15 of 15 evaluable patients, CD80-SA-specific cytotoxic T cell responses against autologous tumors were generated, 11 of which were significant, with specific killing ranging from 5 to 70%. Taken together, these data demonstrate that primary tumor cells can be effectively decorated with CD80-SA and that such cells serve as APCs to induce autologous antitumor T cell responses.

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B7.1 on Human Carcinomas: Costimulation of T Cells and Enhanced Tumor-Induced T-Cell Death

Cited by 19 publications

References 27 publications

Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL

Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

Primary Tumor Cells Resected from Cancer Patients and Decorated with a Novel Form of CD80 Protein Serve as Effective Antigen-Presenting Cells for the Induction of Autologous T Cell Immune Responses Ex Vivo

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