We have investigated Amblyomin-X-treated
horse melanomas to better understand its mode of action through
transcriptome analysis and the in vivo model. Amblyomin-X is a Kunitz-type homologous
protein that selectively leads to the
death of
tumor cells via ER stress and
apoptosis, currently under investigation as a new
drug candidate for
cancer treatment.
Melanomas are immunogenic
tumors, and a better
understanding of the
immune responses is warranted. Equine
melanomas are spontaneous and not so aggressive as
human melanomas are, as this study shows that the in vivo
treatment of encapsulated
horse melanoma tumors led to a significant reduction in the
tumor size or even the complete disappearance of the
tumor mass through intratumoral
injections of Amblyomin-X.
Transcriptome analysis identified ER- and
mitochondria-stress, modulation of the innate
immune system,
apoptosis, and possibly
immunogenic cell death activation. Interactome
analysis showed that Amblyomin-X potentially interacts with key
elements found in
transcriptomics. Taken together, Amblyomin-X modulated the
tumor immune microenvironment in different ways, at least contributing to induce
tumor cell death.