Arsenic trioxide as an inducer of immunogenic cell death
Abstract
Arsenic trioxide (ATO) is often combined with all-trans retinoic acid (ATRA) to treat promyelocytic leukemia (PML) with a rather high success rate. In mice, it has been documented that ATRA is much more efficient against PML developing in immunocompetent than in immunodeficient mice, pleading in favor of the idea that the antileukemic action of ATRA depends on the immune system. However, no such immunedependent effects of ATO have been described in PML. Nonetheless, it has been shown that ATO increases lymphokine activated killer (LAK)-mediated cytotoxicity against human myeloma cells and enhances the efficacy of Bacille Calmette-Guérin (BCG) immunotherapy in a mouse model of bladder cancer. Moreover, ATO has been demonstrated to deplete regulatory T cells in a mouse model of colon cancer. Of note, in a recent paper published in Cellular and Molecular Immunology, Chen et al. demonstrate that ATO can trigger immunogenic cell death (ICD) in solid tumors. The concept of ICD, initially established in cells undergoing apoptosis, has recently been extended to other variants of regulated cell death such as necroptosis, pyroptosis, and ferroptosis. Canonical ICD triggers the emission of a set of danger associated molecular patterns (DAMPs), which act on specific pattern recognition receptors (PRRs) expressed by antigen presenting dendritic cells (DCs), thus stimulating phagocytosis of malignant cells and antigen presentation of tumorassociated antigens by DCs. Mature DCs facilitate…
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