Vigorous Premalignancy-specific Effector T Cell Response in the Bone Marrow of Patients with Monoclonal Gammopathy

Dhodapkar, Madhav V.; Krasovsky, Joseph; Osman, Keren; Geller, Matthew D.

doi:10.1084/jem.20031030

Cited by 194 publications

(178 citation statements)

References 31 publications

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“…In the same view, KM-HN-1 was also expressed in purified plasma cells from 83% of the patients with MGUS, MAGE-C1 in 33%, DDX43 in 33%, and SPACA3, MORC, GAGE1-8, CT45, and SPANXB in 8%. Patients with MGUS continuously transform into MM with an annual rate of ϳ1% (48) and these data may suggest initiating vaccination strategies early in these patients, i.e., when there is still an efficient T cell repertoire against the plasma cell Ags (49).…”

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

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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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

109

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“…Immune responses against autologous myeloma cells were detected in patients with MGUS or asymptomatic PCM. 10,11 The progression of disease was associated with loss of both adaptive and innate immune effector functions, suggesting that disabling of immune surveillance may contribute to progression. However, these myeloma-associated immune responses (IRs) could be restored ex vivo with appropriate stimulation.…”

Section: Introductionmentioning

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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“…Understanding of preneoplastic conditions like monoclonal gammopathy of undetermined significance (MGUS) has helped further to strengthen the belief in equilibrium phase of cancer. The existence of an immune response to premalignant MGUS cells that eventually progress to multiple myeloma (MM) is consistent with the CI equilibrium, with the immune system controlling, but not eliminating, MGUS cells that eventually evolve and progress to malignancy [6,7].…”

Section: First and Foremost Question -Does The Equilibrium Phase Realmentioning

confidence: 64%

“…In the former case the tumor cells enter a state of quiescence or senescence due to unknown mechanisms, whereas in the later they undergo enhanced apoptosis owing to poor vascularisation and hypoxia [2,7].…”

Section: First and Foremost Question -Does The Equilibrium Phase Realmentioning

confidence: 99%

Cancer-Immune Equilibrium: Questions Unanswered

Bhatia

Kumar

2011

Cancer Microenvironment

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Cancer-immune (CI) equilibrium constitutes an important component of the cancer immunoediting theory. It is defined as a period during which our immune system and cancer live in harmony in the body. The immune system, though not able to completely eliminate the cancer, doesn't allow it to progress or metastasize further. Mechanisms of this phase are poorly understood because this phase is difficult to identify even by the most modern detection methods. Till now, the work done on the equilibrium phase of cancer, suggests promising improvements in cancer therapy if the disease could be withheld in this phase. However, there are many queries which remain to be addressed about this interesting yet unresolved phase of cancer immunity.

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Vigorous Premalignancy-specific Effector T Cell Response in the Bone Marrow of Patients with Monoclonal Gammopathy

Cited by 194 publications

References 31 publications

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

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

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

Cancer-Immune Equilibrium: Questions Unanswered

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