title: The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy.
abstract: Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation. The schedule of administration is of special importance for the immunological effect: while cyclophosphamide can be used in high-dose therapy for the complete eradication of haematopoietic cells, lower doses of cyclophosphamide are relatively selective for T cells. Of special interest is the fact that a single administration of low-dose cyclophosphamide is able to selectively suppress regulatory T cells (Tregs). This effect can be used to counteract immunosuppression in cancer. However, cyclophosphamide can also increase the number of myeloid-derived suppressor cells. Combination of cyclophosphamide with other immunomodulatory agents could be a promising approach to treat different forms of advanced cancer.
authors.affiliation: Pädiatrische Hämatologie und Onkologie, Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, A1, Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Ahlmann
authors.affiliation: PharmaCampus, Klinische Pharmazie, Westfälische Wilhelms-Universität Münster, Corrensstraße 48, 48149, Münster, Germany. georg.hempel@uni-muenster.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology; D007166:Immunosuppressive Agents; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: Immune reactivation; Immunosuppression; Oxazaphosphorines; T cells