Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma

Choi, Carmen; Witzens, Mathias; Bucur, Marianna; Feuerer, Markus; Sommerfeldt, Nora; Trojan, Andreas; Ho, Anthony D.; Schirrmacher, Volker; Goldschmidt, Hartmut; Beckhove, Philipp

doi:10.1182/blood-2004-01-0366

Cited by 106 publications

(82 citation statements)

References 21 publications

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“…Correlate data from patients with breast cancer demonstrated that, following adoptive transfer, primed T cells from the BM, but not the peripheral blood (PB), could effectively treat autologous breast cancer xenografts in NOD/SCID mice (8 -10). Similar findings have recently been described for pancreatic tumors (11), myeloma (12), and melanoma (13). Finally, in mouse viral infection models, the BM was found to harbor virus-specific memory CD8 ϩ T cells that could mediate protection from lymphocytic choriomeningitis virus infection when adoptively transferred into naive SCID hosts (14), and virus-specific memory CD8 ϩ T cells were also produced in BM in response to vesicular stomatitis virus infection (5).…”

supporting

confidence: 73%

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Zhang

Dong

Lin

et al. 2006

The Journal of Immunology

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The role of human bone marrow (BM) CD8+ T cells in the immune response to viral Ags is poorly defined. We report here the identification and characterization of a functionally enhanced effector memory CD8+ T cell population (TEM) in the BM of patients undergoing total joint replacement for osteoarthritis. These BM-derived TEM differ strikingly from correlate cells in peripheral blood (PB), expressing elevated levels of CD27, HLA-DR, CD38, CD69, and unique patterns of chemokine receptors. Interestingly, while BM TEM have low levels of resting perforin and granzyme B, these molecules evidence profound up-regulation in response to TCR stimulation resulting in enhanced cytotoxic potential. Moreover, compared with the TEM subset in PB, BM CD8+ TEM cells demonstrate a more vigorous recall response to pooled viral Ags. Our results reveal that human BM serves as a repository for viral Ag-specific TEM with great therapeutic potential in vaccine development.

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supporting

confidence: 73%

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Zhang

Dong

Lin

et al. 2006

The Journal of Immunology

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“…In addition, we will need to identify immunogenic peptides for MORC, DDX43, and MAGE-A5 gene products for which T cell reactivity is not presently demonstrated. Once this immunological work done, i.e., by associating these CT genes peptides with other tumor-associated Ag peptides reported in MM, e.g., MUC-1 or HM-1.24 (61,62), one can envision covering almost all patients in a population with a set of 3-5 individually selected immunogenic peptides.…”

Section: Discussionmentioning

confidence: 99%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

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109

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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“…The high incidence of spontaneous T-cell reactivity against PDAC is in striking contrast to observations from numerous other cancer entities that induced cancerreactive T cells only in 25-60% of the patients. [47][48][49] T-cell responses are regulated by dendritic cells (DCs), which constantly take up antigens in all tissues. Upon in situ activation, antigen-loaded DCs migrate to lymphatic organs to stimulate na€ ıve T cells.…”

Section: Immune Cellsmentioning

confidence: 99%

Pancreatic cancer microenvironment

Kleeff

Beckhove

Espósito

et al. 2007

Intl Journal of Cancer

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193

165

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Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that is virtually therapy‐resistant and has therefore one of the worst prognoses of all human cancers. The focus of research, which had been placed mostly on genetic and epigenetic alterations of the cancer cells themselves, has shifted gradually towards the microenvironment. The cancer microenvironment consists of various components, including fibroblasts, endothelial cells, immune cells, and endocrine cells, that interact with each other and the cancer cells in a complex fashion. This interplay has implications for pancreatic cancer cell growth, migration and invasion, angiogenesis, and immunological recognition of cancer cells. Evidence is accumulating that the cancer microenvironment plays an active role in disease progression, and efforts are being made to target this interplay between cancer cells and host cells to improve the outcome of this deadly disease. © 2007 Wiley‐Liss, Inc.

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Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma

Cited by 106 publications

References 21 publications

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Human Bone Marrow: A Reservoir for “Enhanced Effector Memory” CD8+ T Cells with Potent Recall Function

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Pancreatic cancer microenvironment

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