Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model

We have investigated Amblyomin-X-treated horse melanomas to better understand its mode of action through transcriptome analysis and also 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 are warranted. Equine melanomas are spontaneous and not aggressive as human melanomas are, and we showed that the in vivo treatment of encapsulated horse melanoma tumors led to a significant tumor size reduction or even the complete disappearance of the tumor mass through intratumoral injections of Amblyomin-X. Transcriptome analysis identified ER and mitochondria-stresses, 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, making at least part to induce tumor cell death. This is a time series experiment: control 0h, treatment evolution 6h, 12h. For each time-point, we have 3 animals x 2 tumors = 6 samples. We must discard two samples from 12h, due to low library size.