Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Wen, Yue Jin; Barlogie, Bart; Yi, Qing

doi:10.1182/blood.v97.6.1750

Cited by 116 publications

(81 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cells produce monoclonal immunoglobulins that carry unique antigenic determinants and act as tumor-specific antigens for recognition and destruction of these cells by the immune system (Wen et al, 2001;Galea et al, 2002). Immune responses are tightly regulated by CD4+ T helper (TH) lymphocytes (Cresswell, 1994).…”

Section: Introductionmentioning

confidence: 99%

MHC class II transactivator (CIITA) expression is upregulated in multiple myeloma cells by IFN-γ

Zhao

Flynt

Hong

et al. 2007

Molecular Immunology

View full text Add to dashboard Cite

The MHC Class II transactivator (CIITA) acts in the cell nucleus as the master regulator of MHC class II (MHC II) gene expression. It is important to study CIITA regulation in multiple myeloma since MHC expression is central to ability of myeloma cells to present antigen and to the ability of the immune system to recognize and destroy this malignancy. Regulation of CIITA by IFN-γ in B lymphocytes occurs through the CIITA type IV promoter (pIV), one of the four potential promoters (pI-pIV) of this gene. To investigate regulation of CIITA by IFN-γ in multiple myeloma cells, first the ability of these cells to respond to IFN-γ was examined. RTPCR analyses show that IFN-γR1, the IFN-γ-binding chain of the IFN-γ receptor, is expressed in myeloma cells and IRF-1 expression increases in response to IFN-γ treatment. Western blotting demonstrates that STAT1 is activated by phosphorylation in response to IFN-γ. RT-PCR and functional promoter analyses show that IFN-γ up regulates the activity of CIITA pIV, as does ectopic expression of IRF-1 or IRF-2. In vivo protein/DNA binding studies demonstrate protein binding at the GAS, E box and IRF-E sites. In vitro studies confirm the binding of IRF-1 and IRF-2 to CIITA pIV. Although multiple myeloma cells express PRDI-BF1/Blimp-1, a factor that represses both the CIITA type III and IV promoters, they retain the capability to up regulate CIITA pIV and MHC II expression in response to IFN-γ treatment. These findings are the first to demonstrate that although PRDI-BF1/Blimp-1 diminishes the constitutive ability of these cells to present antigen by limiting CIITA and MHC II expression, it is possible to enhance this expression through the use of cytokines, like IFN-γ.

show abstract

Section: Introductionmentioning

confidence: 99%

MHC class II transactivator (CIITA) expression is upregulated in multiple myeloma cells by IFN-γ

Zhao

Flynt

Hong

et al. 2007

Molecular Immunology

View full text Add to dashboard Cite

show abstract

“…[1][2][3] There is in vitro evidence that T cells recognize myeloma cells and generate antimyeloma activity. [4][5][6] Both T cells and dendritic cells, however, have been shown to be functionally defective. [7][8][9][10][11] This may explain why active specific immunotherapy has fallen short of clinical expectations.…”

Section: Introductionmentioning

confidence: 99%

Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma

Mariani¹,

Muraro²,

Pantaleoni³

et al. 2005

Leukemia

118

115

View full text Add to dashboard Cite

The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vc9/Vd2 (cd) T cells of normal donors and multiple myeloma (MM) patients. cd T cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of cd T cells was observed in 100% of normal donors and 50% of MM patients. cd T cells produced IFN-c, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM cd T cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of cd T cells and by enhancing the immunosensitivity of myeloma cells to cd T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.

show abstract

“…For example, a number of T cell epitopes have been well characterized for human melanoma (1-3), renal cell carcinoma (36), and breast carcinoma (37) antigens. Functional CD4 and CD8 T cell responses against the B cell tumor antigen Id have also been described in patients with different types of B cell malignancies (17,38,39), especially after active immunization with Id protein. However, information on the precise nature of antigenic epitopes in Id protein recognized by the responding T cells is limited.…”

Section: Discussionmentioning

confidence: 99%

Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes

Baskar¹,

Kobrin²,

Kwak³

2004

J. Clin. Invest.

View full text Add to dashboard Cite

Methods Patients , vaccine, and PBMC samples. Patients with advanced FL enrolled on this institutional review board-approved vaccine study were described previously (17). Briefly, patients had received chemotherapy to the first complete remission. Following at least 6 months of immune recovery, they received five subcutaneous injections of autologous, tumor-derived Ig protein conjugated to KLH (Id-KLH), mixed with human recombinant GM-CSF (rGM-CSF). While for FL patients the Id was isolated from heterohybridomas generated by fusion with tumor B cells, for myeloma patients the Id was isolated from patients' serum by affinity chromatography (17). Blood samples were collected from the patients

show abstract

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Cited by 116 publications

References 32 publications

MHC class II transactivator (CIITA) expression is upregulated in multiple myeloma cells by IFN-γ

MHC class II transactivator (CIITA) expression is upregulated in multiple myeloma cells by IFN-γ

Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma

Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes

Contact Info

Product

Resources

About