Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade

Rauch, Daniel A.; Conlon, Kevin C.; Janakiram, Murali; Brammer, Jonathan E.; Harding, John C. S.; Ye, B. Hilda; Zang, Xingxing; Ren, Xiaoxin; Olson, Sydney L.; Cheng, Xiaogang; Miljković, Miloš D.; Sundaramoorthi, Hemalatha; Joseph, Ancy; Skidmore, Zachary L.; Griffith, Obi L.; Waldmann, Thomas A.; Ratner, Lee

doi:10.1182/blood.2019002038

Cited by 86 publications

(62 citation statements)

References 43 publications

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“…One speculates that infected cells differentiate into various hematopoietic cells including T cells, B cells, monocytes, and neutrophils. HTLV-1 infection to immature cells was also suggested by the report that ATL clones with the identical integration site of the provirus and different T-cell receptor gene rearrangement were found in the same patients [64]. It is possible that viral gene(s) modulate the differentiation of infected cells.…”

Section: How Hbz Modulates Infected Cellsmentioning

confidence: 91%

HTLV-1 bZIP factor: the key viral gene for pathogenesis

Matsuoka¹,

Mesnard²

2020

Retrovirology

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Human T cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. The HTLV-1 bZIP factor (HBZ) gene is constantly expressed in HTLV-1 infected cells and ATL cells. HBZ protein suppresses transcription of the tax gene through blocking the LTR recruitment of not only ATF/CREB factors but also CBP/p300. HBZ promotes transcription of Foxp3, CCR4, and T-cell immunoreceptor with Ig and ITIM domains (TIGIT). Thus, HBZ is critical for the immunophenotype of infected cells and ATL cells. HBZ also functions in its RNA form. HBZ RNA suppresses apoptosis and promotes proliferation of T cells. Since HBZ RNA is not recognized by cytotoxic T cells, HTLV-1 has a clever strategy for avoiding immune detection. HBZ plays central roles in maintaining infected T cells in vivo and determining their immunophenotype.

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Section: How Hbz Modulates Infected Cellsmentioning

confidence: 91%

HTLV-1 bZIP factor: the key viral gene for pathogenesis

Matsuoka¹,

Mesnard²

2020

Retrovirology

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“…The molecular mechanism behind this phenomenon remains unknown, but authors detected an increase in cells expressing proliferation marker Ki67 and a decrease in apoptosis marker Caspase-3 [71]. In certain cancers, acute T-cell lymphocytic leukaemia as a prime example, PD-1 is proposed to function as a tumour suppressor [55]. The rapid growth of PD-1 expressing cancer cells after blocking PD-1 suggests its inhibitory role so widely observed in T-cells [73].…”

Section: Pd-1 Intrinsic Signallingmentioning

confidence: 99%

Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model

Kocikowski

Dziubek

Parys

2020

Cancers

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Immune evasion is a major challenge for the development of successful cancer treatments. One of the known mechanisms is the expression of immune checkpoints (ICs)—proteins regulating the immune cells activation. The advent of immunotherapy using monoclonal antibodies (mAbs) to block the immune checkpoint receptor-ligand interaction brought about a landslide improvement in the treatment responses, leading to a prompt approval of such therapeutics. In recent years, it was discovered that a subset of patients receiving IC blockade treatment experienced a previously unknown pattern of treatment response called hyperprogression (HP), characterised by rapid deterioration on initialisation of the therapy. HP represents an urgent issue for clinicians and drug developers, while posing questions about the adequacy of the current clinical trial process. Here, we briefly summarise the state of knowledge and propose new directions for research into HP mechanisms, focusing on tumour-intrinsic signalling of IC proteins malignantly expressed by cancer. We also discuss the potential role of spontaneously occurring canine cancer in the assessment of immunotherapeutics, which can provide the missing link between murine and human studies.

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“…As for the other immunotherapy, immune checkpoint inhibitors such as programmed cell death-1 (PD-1) inhibitors and programmed cell death-ligand 1 (PD-L1) inhibitors are also expected to show high efficacy for patients with ATL. However, it has been reported that patients with indolent ATL progress rapidly after receiving PD-1 inhibitor (nivolumab) therapy [49,50]. In a small Japanese study of patients with aggressive ATL, no patient showed characteristics similar to those in the cases reported by Ratner et al [49][50][51].…”

Section: Remaining Issuesmentioning

confidence: 99%

“…However, it has been reported that patients with indolent ATL progress rapidly after receiving PD-1 inhibitor (nivolumab) therapy [49,50]. In a small Japanese study of patients with aggressive ATL, no patient showed characteristics similar to those in the cases reported by Ratner et al [49][50][51]. An anti-tumor role of the PD-1/PD-L1 pathway might be different between the indolent and aggressive stages of ATL.…”

Section: Remaining Issuesmentioning

confidence: 99%

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

Oka

Matsuoka

Utsunomiya

2020

Cancers

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Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death.

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Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade

Cited by 86 publications

References 43 publications

HTLV-1 bZIP factor: the key viral gene for pathogenesis

HTLV-1 bZIP factor: the key viral gene for pathogenesis

Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

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