Regulation of Dendritic Cell Function with Immunomodulatory Drugs

Mohty, Mohamad; Gaugler, Béatrice; Mami, Naira Ben; Olive, Daniel

doi:10.2174/1568014053507140

Cited by 14 publications

(17 citation statements)

References 77 publications

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“…Two of the subjects within this high-dose cohort (patients 8 and 9) were treated with only a single vaccination due to insufficient numbers of dendritic cells that met the HLA-DR + /CD-14 À lot release criteria. Of note, patient 8 had prior therapy with thalidomide and patient 9 had previously been treated with Neupogen (r-met-Hu-G-CSF), both of which have potential immunomodulatory effects on dendritic cell phenotype/function (31,32).…”

Section: Resultsmentioning

confidence: 99%

Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous System Tumor Microenvironment

Liau

Prins²,

Kiertscher

et al. 2005

Clinical Cancer Research

478

378

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Section: Resultsmentioning

confidence: 99%

Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous System Tumor Microenvironment

Liau

Prins²,

Kiertscher

et al. 2005

Clinical Cancer Research

478

378

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“…Finally, a large number of factors (drugs, cytokines, microbial products) are known to modulate DC activation/ function in the context of eliciting immune responses, and may also have effects on any myeloma/DC interaction. Along these lines, it is interesting to note that both thalidomide and bortezomib, which have significant activity in myeloma, have been shown to modulate DC function 74,75 and induce DC apoptosis. 76 BLOOD, 1 JUNE 2007 ⅐ VOLUME 109, NUMBER 11 For personal use only.…”

Section: Discussionmentioning

confidence: 99%

CD28-mediated regulation of multiple myeloma cell proliferation and survival

Bahlis

King

Kolonias

et al. 2007

Blood

119

115

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Although interactions with bone marrow stromal cells are essential for multiple myeloma (MM) cell survival, the specific molecular and cellular elements involved are largely unknown, due in large part to the complexity of the bone marrow microenvironment itself. The T-cell costimulatory receptor CD28 is also expressed on normal and malignant plasma cells, and CD28 expression in MM correlates significantly with poor prognosis and disease progression. In contrast to T cells, activation and function of CD28 in myeloma cells is largely undefined. We have found that direct activation of myeloma cell CD28 by anti-CD28 mAb alone induces activation of PI3K and NFB, suppresses MM cell proliferation, and protects against serum starvation and dexamethasone (dex)-induced cell death. Coculture with dendritic cells (DCs) expressing the CD28 ligands CD80 and CD86 also elicits CD28-mediated effects on MM survival and proliferation, and DCs appear to preferentially localize within myeloma infiltrates in primary patient samples. Our findings suggest a previously undescribed myeloma/DC cell-cell interaction involving CD28 that may play an important role in myeloma cell survival within the bone marrow stroma. These data also point to CD28 as a potential therapeutic target in the treatment of MM. IntroductionMultiple myeloma (MM) remains an incurable clonal B lymphoid neoplasm of plasma cells, second only to non-Hodgkin lymphoma in incidence. 1 Despite significant initial responses to chemotherapy, more than 90% of patients with MM relapse with resistant disease, 2 underscoring the need to identify novel therapeutic targets that affect myeloma survival and resistance pathways. Given that MM cells are critically dependent on normal elements of the bone marrow stroma for cell growth and survival, these interactions are attractive targets. One such interaction is stromal production of soluble growth factors, such as IL-6 and TRANCE. 1,3 Another important set of interactions involves direct myeloma cell contact with extracellular matrix (ECM) and/or stromal cells. Such direct contact up-regulates stromal cell IL-6 and VEGF production, induces NFB signaling, drops myeloma cells out of cell cycle, and enhances resistance to chemotherapy. [4][5][6] However, the specific molecular (eg, integrins 4,7 ) and cellular components (eg, osteoclasts 8 ) of these direct interactions within the complex bone marrow microenvironment are only beginning to be described. As important, the characteristic progression of myeloma to stromal independence marks a clinically worse disease, 9 yet the mechanisms that underlie this transition are also poorly understood.Identification of prosurvival receptors typically expressed on myeloma cells may point to the stromal cells expressing the receptor ligands. One potential receptor is CD28. CD28 has a restricted lineage expression, found predominantly on T cells but also on normal plasma cells, primary myeloma isolates, and myeloma cell lines at levels comparable with T cells. [10][11][12][13] In T cells, CD28 recep...

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“…The response to thalidomide was postulated to be more due to the augmentation of GVM effects than antitumor effects. 39,40 Similarly, a patient with relapsed/refractory EM PCM post-allogeneic HCT attained CR with bortezomib also by enhancing GVM effects. 41 In a randomized phase III trial, the Spanish Myeloma Group assessed induction chemotherapy before autologous HCT in newly diagnosed PCM patients, 18% of whom had EM PCM at diagnosis.…”

Section: Chemotherapymentioning

confidence: 99%

“…However, thalidomide and bortezomib may have also potentiated the GVM effect at the EM sites. 40,47 Furthermore in the report by Zeiser et al 19 PCM patients with EM relapse received DLI alone and achieved responses similar to those with IM relapse signifying the impact of GVM effects at EM sites. For example, a PCM patient with multiple subcutaneous plasmacytomas after allogeneic HCT responded to DLI with durable CR.…”

mentioning

confidence: 95%