Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma

Tamura, Hideto; Ishibashi, Mariko; Yamashita, Takenari; Tanosaki, Sakae; Okuyama, Namiko; Kondo, Asaka; Hyodo, Hideya; Shinya, Eiji; Takahashi, Hidemi; Dong, Haidong; Tamada, Koji; Chen, L; Dan, Kazuo; Ogata, Kíyoyuki

doi:10.1038/leu.2012.213

Cited by 211 publications

(227 citation statements)

References 44 publications

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“…In addition, PD-L1 directly promotes myeloma progression, as PD-L1 + myeloma cells display an increased proliferation rate and resistance to chemotherapy compared to PD-L1 − myeloma cells. In accordance with these in vitro observations, high levels of PD-L1 on myeloma cells in patients are associated with an increased myeloma infiltration in their bone marrow and signs of clinical progression [32].…”

Section: T Cellssupporting

confidence: 63%

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Binsfeld

Fostier

Muller

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy. In this review, we summarize the immune cell changes that occur in multiple myeloma patients and we discuss the cell-based immunotherapies that have been tested in multiple myeloma, with a focus on murine models.

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Section: T Cellssupporting

confidence: 63%

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Binsfeld

Fostier

Muller

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…41 PD-L1 is expressed on primary myeloma cells from PCM patients, and several studies have demonstrated that blockade of the PD-1/PD-L1 axis augments T and NK cell-mediated antimyeloma activity in vitro as well as in murine myeloma models. 17,[42][43][44][45] These antimyeloma effects can be further enhanced by combining PD-1/PD-L1 blockade with irradiation, cell-based vaccines, hematopoietic stem cell transplant or lenalidomide, 17,46,47 providing a rationale for combination therapy trials. A phase I trial of the anti-PD-1 Ab nivolumab in various hematologic malignancies included 27 relapsed/refractory PCM patients and demonstrated prolonged stable disease in twothirds.…”

Section: Pd-1/pd-l1 Checkpoint Inhibitorsmentioning

confidence: 99%

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

Lendvai

Cohen

Cho

2015

Bone Marrow Transplant

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Autologous hematopoietic cell transplantation (auto-HCT) is the standard consolidation therapy for plasma cell myeloma patients following induction therapy. Auto-HCT improves disease-free survival (DFS), but is generally not curative. The allogeneic HCT experience demonstrated that T-cell immunotherapy can confer long-term DFS. Preclinical and clinical data indicate that myelomaassociated Ags elicit humoral and cellular immune responses (IRs) in myeloma patients. These findings strongly suggest that the immunotherapeutic strategies, including immune checkpoint inhibitors, therapeutic cancer vaccines and adoptive cellular therapies, are promising avenues of clinical research that may be most applicable in the minimal residual disease state following auto-HCT. These strategies are designed to prime or augment antimyeloma IRs and promote a 'host-vs-myeloma' effect that may result in durable DFS. Innovative clinical trials investigating immune checkpoint inhibitors and cancer vaccines have demonstrated that robust immunity against myeloma-associated Ags can be elicited in the setting of auto-HCT. A diverse array of immunotherapeutic strategies have entered clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further investigation of combinations of immunologic and pharmaceutical agents are expected in the near future. In this review, we will discuss the preclinical data supporting immunotherapy in auto-HCT for myeloma, clinical investigation of these strategies and the future prospects of immunotherapy in pursuit of the goal of curative therapy.

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“…IFN-g and IL-6 have also been reported to induce PD-L1 expression in MM cells. 27,28 We next compared the effect of IFN-g, IL-6, and APRIL on PD-L1 expression by immunoblotting. All these cytokines enhanced PD-L1 expression in MM1R and JJN3 MM cells, associated with cytokine-induced phosphorylation of MEK1/2 ( Figure 4F).…”

Section: Galectin-9 Induces Apoptosis Of Human T Cells But Not MM Celmentioning

confidence: 99%