title: Low dose cyclophosphamide: Mechanisms of T cell modulation.
abstract: Cyclophosphamide is considered one of the most successful chemotherapy drugs and is listed on the World Health Organisations List of Essential Medicines. Since its initial synthesis in 1958, it has been widely used to treat a range of cancers but its use has been declining due to the advent of platinum based and other chemotherapy agents. However, cyclophosphamide is still used either as a single agent or as adjuvant therapy to treat lymphomas, and breast and ovarian cancers at much lower doses. The efficacy of low dose cyclophosphamide is primarily due to its ability to promote anti-tumour immunity, by selectively depleting regulatory T cells and enhancing effector T cell function. Compared to effecter T cells, regulatory T cells have metabolic adaptations that make them more susceptible to cyclophosphamide-mediated cytotoxicity. In this review, we highlight the potential for improving the efficacy of low dose cyclophosphamide by combining insights on the mechanisms of cyclophosphamide-mediated cytotoxicity, and how these cytotoxic effects of cyclophosphamide influence T cell function, thereby contributing to anti-tumour immunity.
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University, Melbourne, Australia.
authors.forename: Mutsa Tatenda
authors.initials: MT
authors.lastname: Madondo
authors.affiliation: Womens Cancer Research Centre, Royal Women's Hospital, Melbourne, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Quinn
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department of Immunology and Pathology, Monash University, Melbourne, Australia. Electronic address: magdalena.plebanski@monash.edu.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000171:Acrolein / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D002453:Cell Cycle / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D018384:Oxidative Stress; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003432:Cross-Linking Reagents; D011355:Prodrugs; D000171:Acrolein; D000255:Adenosine Triphosphate; D003520:Cyclophosphamide
keywords: Acrolein; Chemotherapy; Cyclophosphamide; GSH; T cells