Title:Use of Anti-Cancer Drugs, Mitocans, to Enhance the Immune Responses against Tumors
Volume: 14
Issue: 3
Author(s): T. Hahn, M. J. Polanczyk, A. Borodovsky, L. V. Ramanathapuram, E. T. Akporiaye and S. J. Ralph
Affiliation:
Keywords:
Mitocans, immunotherapy, inflammasome, cancer therapy, reactive oxygen species, mitochondria
Abstract: Cytotoxic drugs in cancer therapy are used with the expectation of selectively killing and thereby eliminating
the offending cancer cells. If they should die in an appropriate manner, the cells can also release danger signals that promote
an immune reaction that reinforces the response against the cancer. The identity of these immune-enhancing danger
signals, how they work extra- and intracellularly, and the molecular mechanisms by which some anti-cancer drugs induce
cell death to bring about the release of danger signals are the major focus of this review. A specific group of mitocans, the
vitamin E analogs that act by targeting mitochondria to drive ROS production and also promote a more immunogenic
means of cancer cell death exemplify such anti-cancer drugs. The role of reactive oxygen species (ROS) production and
the events leading to the activation of the inflammasome and pro-inflammatory mediators induced by dying cancer cell
mitochondria are discussed along with the evidence for their contribution to promoting immune responses against cancer.
Current knowledge of how the danger signals interact with immune cells to boost the anti-tumor response is also
evaluated.