A team of researchers at the Ludwig Cancer Research Institute has unveiled a specific cellular mechanism in which the resistant melanomas (the ones failing to respond to checkpoints blockade) can be made susceptible to the immunotherapy.
The study was led by Ping-Chih Ho –Assistant Professor at the University of Lausanne. The reports of the study were published in the journal named Nature Immunology and aim at identifying the existing drug for diabetes that can be used for accomplishing the purpose.
The specialized checkpoint inhibitors or blockade therapies have been designed for lifting the limitations that are imposed on the immunity responses by the body. The checkpoint inhibitors work upon by attacking the cancer tumors with the help of the killer T-cells belonging to the immune system of the body.
In the given study, the team of researchers engrafted mice having melanoma (the tumors in mice were known to resist the specific checkpoint blockade anti-PD-1). After the induction of UCP2 expression in the given tumors and treating the tumors in mice with the anti-PD-1 drug helped in eliciting robust immune responses that were anti-tumor and significantly helped in extending the overall survival of mice. The boosted immunity also reacted to the tumor microenvironment with restriction. This, in turn, attenuated the risk associated with the respective checkpoint blockade. The risk was the provocation of autoimmune responses in the body that can damage the healthy tissues –sometimes leading to a lethal effect.
In the given research, the researchers identified “rosiglitazone” – an anti-diabetic drug that is known for inducing UCP2 expression. When the tumor-induced mice were treated with this anti-diabetic drug, it transformed the hot tumors into cold tumors by sensitizing them to the checkpoint blockade and extending the overall survival in mice. The team of researchers also found that the drug was capable of inducing UCP2 expression in specific melanoma cell cultures that were obtained from the patients.
Ho states, “The results of the research explain that the drug that is responsible for activating the pathway can help in improving the therapeutic results of the treatment associated with checkpoint blockade.” He adds, “The UCP2 expression protein might also serve as the diagnostic milestone of ensuring a positive response to the treatment of checkpoint blockade. This is what we are currently working on.”
The team of researchers also confirm that the respective results of the preclinical studies can help in supporting the trial that can improve the checkpoint inhibitor therapy.
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