Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Vučković, Slavica; Minnie, Simone A.; Smith, David C.; Gartlan, Kate H.; Watkins, Thomas S.; Markey, Kate A.; Mukhopadhyay, Pamela; Guillerey, Camille; Kuns, Rachel D.; Locke, Kelly R.; Pritchard, Antonia L.; Johansson, Peter; Varelias, Antiopi; Zhang, Ping; Huntington, Nicholas D.; Waddell, Nicola; Chesi, Marta; Miles, John J.; Smyth, Mark J.; Hill, Geoffrey R.

doi:10.1172/jci98888

Cited by 51 publications

(81 citation statements)

References 75 publications

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“…Since Th17 cells have been suggested to induce myeloma progression through IL-17 production (11), Vuckovic and colleagues undertook the task to elucidate the role of IL-17 after autologous transplantation. In this setting, myeloma development was impaired following IL-17 neutralization, confirming the negative impact of IL-17 on disease control (7). The effect of IL-17 is probably not due to its action on the donor graft, as the study by Vuckovic et al showed that transplantation with IL-17 receptor-deficient donor BM did not notably reduce disease burden.…”

Section: Mechanisms Of Autologous Gvt In MMsupporting

confidence: 59%

“…In contrast to clinical observations, Vuckovic et al found that CD8 + T cells, rather than CD4 + T cells or NK cells, are critical for autologous GVT (7). This observation raises the question as to whether this discrepancy is due to the murine model and/or the tumor clone used.…”

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 82%

“…In this issue, Vuckovic et al used the Vk*-MYC murine myeloma model to examine spontaneous T cell antimyeloma immunity in the autologous transplant setting (7). Bone marrow transplantation (BMT) with myeloma-experienced BM performed in myeloma-bearing mice induced clonespecific, T cell-dependent disease control.…”

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 99%

“…Vuckovic and colleagues showed that IFN-γ is critical for the CD8 + T cells to control myeloma. On the other hand, IFN-γ has also been shown to induce PD-L1 expression on ovarian cancer cells, leading to immune eva-gesting that antigen experience contributes to antitumor immunity (7). Mice that received myeloma-experienced CD44 + T cells were found to have an expansion of CD8 + T cells but not CD4 + T cells.…”

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 99%

See 3 more Smart Citations

Autologous graft versus myeloma: it’s not a myth

Dong¹,

Ghobrial²

2018

Journal of Clinical Investigation

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Section: Mechanisms Of Autologous Gvt In MMsupporting

confidence: 59%

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 82%

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 99%

Section: Mechanisms Of Autologous Gvt In MMmentioning

confidence: 99%

See 2 more Smart Citations

Autologous graft versus myeloma: it’s not a myth

Dong¹,

Ghobrial²

2018

Journal of Clinical Investigation

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“…Multiple myeloma (MM) is a malignant disorder of bone marrow plasma cells that is characterized by uncontrolled accumulation and growth of aberrant bone marrow malignant plasma cells, which lead to monoclonal immunoglobulin (Ig) overproduction and decreased normal Igs in the blood, resulting in severe immunodeficiency, bone destruction, and impaired normal hematopoietic function. [1][2][3][4] Naive CD4-positive (CD4 þ ) T cells were divided into 4 major subtypes: T helper (Th)1, Th2, T regulatory (Treg), and Th17 cells. 5 Th17 cells are a recently described CD4 þ T-cell subset that protects hosts against fungal and parasitic infections and participates in inflammatory reactions and autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma

Zhang

Zhou

et al. 2020

Clinical Lymphoma Myeloma and Leukemia

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T helper 17 (Th17) cells changed with different treatment stages of multiple myeloma (MM). The level of Th17 cells in the newly diagnosed group was higher than that in the controls. MM patients with normal Th17 cell levels had the shortest time to complete remission, the highest complete remission rate and the longest progression-free survival. Th17 cell level in newly diagnosed MM patients can be used as a prognostic indicator. Background: T helper 17 (Th17) cells are a subset of CD4-positive T cells, which secrete interleukin 17 and specifically express the retinoic acid receptor-related orphan receptors gt gene. Recently, Studies have shown that the level of Th17 cells in peripheral blood of newly diagnosed multiple myeloma (MM) patients is significantly higher than that of healthy persons. Th17 cells play an important role in the immune microenvironment of MM and interact with tumor cells, osteoclasts, and osteoblasts. Th17 cells might be a potential therapeutic target for MM patients. Patients and Methods: In this study, we further tracked the levels of Th17 cells in peripheral blood of 56 patients with MM from newly diagnosed to partial remission to complete remission to relapse and 11 healthy donors. Results: The level of Th17 cells increased further when the disease reached partial remission, decreased to normal level when it reached complete remission, and increased again when the disease recurred. In addition, we also found that in newly diagnosed MM patients, Th17 cell levels fluctuated greatly; not all patients were upregulated, and patients with normal Th17 cell levels had the highest chance of complete remission. Conclusion: Th17 cells contribute to the stratification of different treatment stages of MM patients. The level of Th17 cells in patients with newly diagnosed MM is associated with the treatment outcome of complete remission.

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T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

Wang

Zhao

et al. 2021

Clinical & Translational Med

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Amyloid light‐chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single‐cell level of CD3 + T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara‐BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8 + T cells. In particular, we found the presence of CD8 + BM resident memory T cells (T RM ) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara‐BCD, these T RM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara‐based therapy in patients with AL amyloidosis promotes anti‐tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis.

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Bone marrow transplantation generates T cell–dependent control of myeloma in mice

Cited by 51 publications

References 75 publications

Autologous graft versus myeloma: it’s not a myth

Autologous graft versus myeloma: it’s not a myth

A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab‐based therapy

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