Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia

Wen, Xuerong; Li, Xiaoxia; Quan, Lina; Yao, Jiying; Mu, Guannan; Guo, Jingjie; Wang, Yitong

doi:10.1080/10428194.2017.1346253

Cited by 9 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…593,594 Corroboratively, Xu et al showed impaired T reg function in peripheral blood of ATO-treated APL patients, although, in this case, a potential involvement of altered redox stress was not investigated. 425 Furthermore, reduced pulmonary metastasis of colon carcinoma cells by ATO was accompanied by reduced T reg infiltration in metastatic nodules. 596 In a follow-up study by the same group, this finding was harnessed for a combination approach of ATO with adoptive T cell transfer, yielding synergistic antimetastatic effects in the same model of colon carcinoma colonization to the lungs.…”

Section: Arsenic (As)mentioning

confidence: 95%

“…Interestingly, in this study, immune-stimulatory effects were achieved at doses (0.5–1 μM) lower than would be required for cancer cell death induction in vitro (2 μM). Similar effects have also been demonstrated in independent reports. , Corroboratively, Xu et al showed impaired T reg function in peripheral blood of ATO-treated APL patients, although, in this case, a potential involvement of altered redox stress was not investigated . Furthermore, reduced pulmonary metastasis of colon carcinoma cells by ATO was accompanied by reduced T reg infiltration in metastatic nodules .…”

Section: Immunological Effects Of Specific Metal Drugsmentioning

confidence: 97%

“…14 So the question arises, how these regulatory immune cell compartments might be specifically targeted to reverse the immune-restrictive cancer microenvironment and re-establish immune surveillance. Surprisingly, solid evidence exists that regulatory immune cell compartments might be highly sensitive against cytotoxic chemotherapy especially with metal drugs including Pt but also As compounds 424,425 (compare section 3.1 and 3.2), while unfortunately for many promising metal drug families no data about this important aspect have been established so far. The mechanisms underlying this hypersensitivity against metal drugs are not completely understood and might be multifactorial.…”

Section: Anticancer Metal Drugs and The Immunementioning

confidence: 99%

See 2 more Smart Citations

Metal Drugs and the Anticancer Immune Response

et al. 2018

View full text Add to dashboard Cite

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.

show abstract

Section: Arsenic (As)mentioning

confidence: 95%

Section: Immunological Effects Of Specific Metal Drugsmentioning

confidence: 97%

Section: Anticancer Metal Drugs and The Immunementioning

confidence: 99%

See 1 more Smart Citation

Metal Drugs and the Anticancer Immune Response

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Tregs are important CD4 + T cells mediating immune tolerance. in vitro tests show that As 2 O 3, at the same concentration, preferentially induces apoptosis of human purified CD4 + CD25 + Tregs than CD4 + CD25 − effector T cells and decreases the Treg frequency in APL patients' peripheral blood (Xu et al, 2018). As 2 O 3 ‐mediated selective Treg depletion was also reported in vivo in a mouse model (Thomas‐Schoemann et al, 2012).…”

Section: The Multifaceted Effects Of Trivalent Arsenic On Immune Cellsmentioning

confidence: 99%

Old dog, new trick: Trivalent arsenic as an immunomodulatory drug

Gaugler

Mohty

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Trivalent arsenic (As(III)) is recently found to be an immunomodulatory agent. As (III) has therapeutic potential in several autoimmune and inflammatory diseases in vivo.In vitro, it selectively induces apoptosis of immune cells due to different sensitivity. At a non-toxic level, As(III) shows its multifaceted nature by inducing either pro-or anti-inflammatory functions of immune subsets. These effects are exerted by either As(III)-protein interactions or as a consequence of As(III)-induced homeostasis imbalance. The immunomodulatory properties also show synergistic effects of As(III) with cancer immunotherapy. In this review, we summarize the immunomodulatory effects of As(III), focusing on the effects of As(III) on immune subsets in vitro, on mouse models of immune-related diseases, and the role of As(III) in cancer immunotherapy.Updates of the mechanisms of action, the pioneer clinical trials, dosing, and adverse events of therapeutic As(III) are also provided.

show abstract

“…ATO-induced Treg depletion appeared to be dependent on “oxidative and nitrosative bursts.” Consistent with these observations, the authors found that in a model of colon cancer, a reduction in tumor volume was observed in immunocompetent but not athymic NUDE mice (123). Xu et al examined the effect of ATO treatment on Treg from APL patients and likewise found that the number and function of Treg was attenuated by ATO treatment (124). ATO has also been reported to up-regulate NK ligands on tumor cells (125) modulate NK cell receptors toward enhanced NK cell mediated cytolytic activity (126).…”

Section: Immunomodulation and Anti-leukemia Therapymentioning

confidence: 99%

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

2019

View full text Add to dashboard Cite

AML holds a unique place in the history of immunotherapy by virtue of being among the first malignancies in which durable remissions were achieved with “adoptive immunotherapy,” now known as allogeneic stem cell transplantation. The successful deployment of unselected adoptive cell therapy established AML as a disease responsive to immunomodulation. Classification systems for AML have been refined and expanded over the years in an effort to capture the variability of this heterogeneous disease and risk-stratify patients. Current systems increasingly incorporate information about cytogenetic alterations and genetic mutations. The advent of next generation sequencing technology has enabled the comprehensive identification of recurrent genetic mutations, many with predictive power. Recurrent genetic mutations found in AML have been intensely studied from a cell intrinsic perspective leading to the genesis of multiple, recently approved targeted therapies including IDH1/2-mutant inhibitors and FLT3-ITD/-TKD inhibitors. However, there is a paucity of data on the effects of these targeted agents on the leukemia microenvironment, including the immune system. Recently, the phenomenal success of checkpoint inhibitors and CAR-T cells has re-ignited interest in understanding the mechanisms leading to immune dysregulation and suppression in leukemia, with the objective of harnessing the power of the immune system via novel immunotherapeutics. A paradigm has emerged that places crosstalk with the immune system at the crux of any effective therapy. Ongoing research will reveal how AML genetics inform the composition of the immune microenvironment paving the way for personalized immunotherapy.

show abstract

Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia

Cited by 9 publications

References 20 publications

Metal Drugs and the Anticancer Immune Response

Metal Drugs and the Anticancer Immune Response

Old dog, new trick: Trivalent arsenic as an immunomodulatory drug

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

Contact Info

Product

Resources

About