Use of anti-cancer drugs, mitocans, to enhance the immune responses against tumors.
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.
School of Medical Sciences, Griffith Health Institute, Griffith University, Parklands Ave., Gold Coast, Queensland 4222, Australia.
T
T
Hahn
M J
MJ
Polanczyk
A
A
Borodovsky
L V
LV
Ramanathapuram
E T
ET
Akporiaye
S J
SJ
Ralph
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death; D007167:Immunotherapy; D058847:Inflammasomes; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D017382:Reactive Oxygen Species / Q000276:immunology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D058847:Inflammasomes; D017382:Reactive Oxygen Species; D014810:Vitamin E