A Novel Therapy for Melanoma Developed in Mice: Transformation of Melanoma into Dendritic Cells with Listeria monocytogenes

Abstract

Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used in cancer immunotherapy because of its capacity to induce a specific cytotoxic T cell response in tumours. This bacterial pathogen strongly induces innate and specific immunity with the potential to overcome tumour induced tolerance and weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma based in its tropism for these tumour cells and its ability to transform in vitro and in vivo melanoma cells into matured and activated dendritic cells with competent microbicidal and antigen processing abilities. This Listeria based vaccination using low doses of the pathogen caused melanoma regression by apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent and implies the reduction of LLO-specific CD4+ T cell responses, strong stimulation of innate pro-inflammatory immune cells and a prevalence of LLO-specific CD8+ T cells involved in tumour regression and Listeria elimination. These results support the use of low doses of pathogenic Listeria as safe melanoma therapeutic vaccines that do not require antibiotics for bacterial removal.

GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

“…At E16 stage, normally neural crest derivatives such as neurons, glial cells or melanoblasts start migration from the neural tube to brains or skin, respectively [ 45 ]. It is possible that LM infection causes impairment of melanoblast migration at this stage, since LM targets to melanocytes and induces apoptosis [ 46 ]. Moreover, other immature features, such as non-distended stomach, collapsed lung and reduction of blood vessels in the lungs and brain, are consistent with arterial ischaemic stroke and foetal bradycardia in early postnatal death [ 3 , 36 , 44 ].…”

Advances in Immunotherapy for Melanoma: A Comprehensive Review

“…Bronchalo-Vicente et al [ 28 ] highlighted the adjuvant properties of listeriolysin O (LLO) (a hemolysin secreted by Listeria monocytogenes , the pathogen that causes listeriosis), such as activation of DCs, stimulation of potent cytotoxic T cells disrupting the immune response to tumors, and enhancement of Th1-dominant immune responses ( Figure 4 ) [ 29 ].…”

“…The percentages of Tregs showing the phenotype CD4 + CD25 high FoxP3 + were also decreased in the TILs of melanoma after administration of the DC-LLO vaccine [ 30 ]. In summary, DC-LLO vaccinations promote stronger antimelanoma immune responses, increase the positive signals between DCs and T cells, and control tumor growth and dissemination [ 28 , 30 ].…”

Dendritic cell therapy in melanoma

“…A different action supposes the use of Listeria against melanoma. This rare human bacterial pathogen induced apoptosis of melanoma cells, even at very low doses and expands CD8 + T cell cytotoxic responses, benefiting also the expansion of melanoma specific cytotoxic responses (26). Moreover, DC loaded with LLO 91-99 peptides can act as recall antigens that pre-condition the vaccination sites and induced anti-tumour immune responses (27).…”