Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts

Dieu, Rifca Le; Taussig, David; Ramsay, Alan G.; Mitter, Richard; Miraki-Moud, Faridah; Fatah, Rewas; Lee, Abigail M.; Lister, T. Andrew; Gribben, John G.

doi:10.1182/blood-2009-02-206946

Cited by 206 publications

(189 citation statements)

References 29 publications

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“…These data are in accordance with the results of Le Dieu et al 16 This suggests that the appearance of a malignant clone in AL patients could trigger an immune response, similar to the increases in WBC count and C-reactive protein level that occur in common infections, which return to normal when the infection is controlled. CD3 + CD56 + T lymphocyte numbers were also affected by WBC counts.…”

Section: Discussionsupporting

confidence: 92%

“…14, 15 We therefore compared the numbers and cytotoxicities of CD3 + CD56 + T lymphocytes in patients with primary AL, healthy controls, and in AL patients who achieved complete remission (CR-AL) following chemotherapy. Only one previous study addressed the issue of CD3 + CD56 + T lymphocyte numbers in the PB at the time of diagnosis of AML, 16 but no previous studies have investigated these factors at the time of diagnosis of ALL, and at the time of complete remission from AL. Similarly, no studies have examined changes in CD3 + CD56 + T lymphocyte numbers and cytotoxicities in AL patients in relation to changes in white blood cell (WBC) counts.…”

Section: Discussionmentioning

confidence: 99%

“…This is supported by the observation in our hospital that patients who did not receive SCT after consolidation chemotherapy frequently relapsed within one year, and were unable to achieve CR with subsequent chemotherapy, developing refractory leukemia. Le Dieu et al 16 showed that CD3 + CD56 + T lymphocytes are not true NKT cells, though a review of the literature [17][18][19][20][21] suggested that CD3 + CD56 + T lymphocytes may include several subsets, including NKT and cytokine-induced killer cells (CIK). increased in AL compared with healthy controls, they were unable to prevent disease progression.…”

Section: Numbers Of Cd3mentioning

confidence: 99%

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Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Guo

Chen

Dong

et al. 2013

Cancer Biology & Therapy

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Numbers Of Cd3mentioning

confidence: 99%

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Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Guo

Chen

Dong

et al. 2013

Cancer Biology & Therapy

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“…The effector memory phenotype CD45RA 2 CD27 2 was predominant in the multiple myeloma gd T cells that proliferated in response to zoledronate, whereas "late" effector cells (CD45RA + CD27 2 ) were predominant in those that failed to expand (32). The skewed effector profile observed here resembles the phenotype previously observed on ab CD3 + CD8 + T cells from newly diagnosed AML (33). Although the authors did not evaluate the cytotoxic function of ab CD3 + CD8 + T cells against autologous blasts, these cells showed the hallmarks of effector cytotoxic T cells (33).…”

Section: Discussionsupporting

confidence: 74%

Human Vγ9Vδ2 T Cells Specifically Recognize and Kill Acute Myeloid Leukemic Blasts

Gertner-Dardenne

Castellano

Mamessier

et al. 2012

The Journal of Immunology

117

101

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Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment.

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“…39,40 Alternatively, tumor-mediated defects in the expression and function of natural killer cells and T cells are reported in AML. 41,42 Relapse after HCT underscores the vagaries of these diseases, the challenges of obtaining long-term cures and the importance of bolstering the native or donor immune system in the relapsed setting.…”

Section: Consolidationmentioning

confidence: 99%

The devil is in the T cells: relapsing after haploidentical hematopoietic cell transplantation

Byrne

Savani

2016

Bone Marrow Transplant

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For several decades, allogeneic hematopoietic cell transplantation (HCT) has remained an important tool in the management of patients with high-risk hematological malignancies. Reduced intensity conditioning regimens and advances in supportive care have improved the safety and accessibility of HCT and also increased the need for a deep and diverse stem cell donor pool. This demand has highlighted existing disparities in the unrelated donor registry, particularly for ethnic minorities, who face significant challenges in identifying HLA-matched adult donors. 1 The acceptance of umbilical cord blood and haploidentical grafts as viable 'alternative' donors has increased the options for these patients and now ensures that a donor can be identified for virtually all patients.The utilization of haploidentical grafts represents appealing options owing to their ubiquity, low cost and donor availability for future lymphocyte accession compared with umbilical cord blood units. Haploidentical grafts, however, lack the long-term follow-up of traditional stem cell sources resulting in several areas where the optimal management strategy remains unknown. With a growing number of patients receiving HCTs from haploidentical sources in the United States and abroad, advancing the care of these patients represents an area of tremendous interest and clinical necessity. 2 Two decades ago, Beatty et al. 3 first reported their experience with HLA-disparate allografts. The patients had high rates of graft rejection and acute GVHD (aGVHD) that was nearly double the HLAmatched control group. Over the following decade, animal studies with post-HCT cyclophosphamide demonstrated encouraging results and gave way to two early-phase studies. [4][5][6] Mechanistically, post-transplant cyclophosphamide reduces the robust, alloantigendirected, naive T-lymphocyte population after stem cell infusion. 7 With posttransplant cyclophosphamide, the rates of aGVHD are substantially reduced. 8,9 Subsequent work in 2008 confirmed minimal aGVHD; however, more than half of patients relapsed within 1 year and 2-year overall survival was a staggering 36%. 10 Parallel, multicenter trials were published 3 years later comparing double umbilical cord blood units with haploidentical grafts. After a median follow-up of 357 days, 45% of haploidentical patients relapsed and 62% were still alive 1 year after HCT. 11 The use of post-transplant cyclophosphamide was championed as a measure that advanced the safety of haploidentical HCT through diminished rates of aGHVD. GVHD, and the coveted GVL effects, are dogmatically linked and drive the long-term remissions seen in survivors. 12,13 In spite of these low rates of aGVHD, improvements in the post-HCT management of these patients translated into improved clinical outcomes. 10,[14][15][16][17][18][19][20][21][22][23][24] Relapsed disease is a principal threat to these patients' longterm survival and affects 30-50% of our patients. [25][26][27] Relapse is driven by an aggressive disease biology that can be difficult and in m...

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Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts

Cited by 206 publications

References 29 publications

Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Human Vγ9Vδ2 T Cells Specifically Recognize and Kill Acute Myeloid Leukemic Blasts

The devil is in the T cells: relapsing after haploidentical hematopoietic cell transplantation

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Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts

Cited by 206 publications

References 29 publications

Numbers and cytotoxicities of CD3+CD56+T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Numbers and cytotoxicities of CD3+CD56+T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Human Vγ9Vδ2 T Cells Specifically Recognize and Kill Acute Myeloid Leukemic Blasts

The devil is in the T cells: relapsing after haploidentical hematopoietic cell transplantation

Contact Info

Product

Resources

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Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia

Numbers and cytotoxicities of CD3⁺CD56⁺T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia