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

Abstract

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.

Plasmacytoid dendritic cell biology and its role in immune‐mediated diseases

“…Arsenic trioxide (As 2 O 3 ), a well‐established drug for acute promyelocytic leukaemia, was observed to have therapeutic potential in pre‐clinical mouse models of SLE, 155 SSc 156 and sclerodermatous GVHD, 157 with unknown mechanism 158 . Our group has recently offered a potential explanation by demonstrating that clinically relevant concentrations of As 2 O 3 preferentially block IFN‐α secretion from pDCs through IRF7 inhibition and also impair the capacity of pDCs to induce T‐/B‐cell responses 159 .…”

PEG-grafted arsenic trioxide-loaded mesoporous silica nanoparticles endowed with pH-triggered delivery for liver cancer therapy

“…ATO may also induce the expression of molecules on the surface of tumor cells that make them more visible to the immune system, leading to increased recognition and elimination of the tumor cells by immune cells. 77 Based on the above results, we can speculate that MSN and ATO can synergistically activate anti-tumor immune responses. The possible mechanism is that, on one hand, MSN acting as an immune stimulator with certain immune activity can also create a chronic, sustained inflammatory response.…”

“…ATO may also induce the expression of molecules on the surface of tumor cells that make them more visible to the immune system, leading to increased recognition and elimination of the tumor cells by immune cells. 77…”

Significance of dietary quinoa husk (Chenopodium quinoa) in gene regulation for stress mitigation in fish

“…The toxicity of arsenic depends on its chemical form, with arsenic pentavalent (As(V)) being highly toxic and trivalent arsenic (As (III)) demonstrating therapeutic potential for autoimmune and inflammatory diseases (Kumar et al 17 ). Over 200 million people in countries such as India, Bangladesh, Argentina, China, Ghana, the USA, and Vietnam face a high risk of arsenic exposure 24 , 25 .…”