Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Authors

  • Mariana S. Nars,

    1. Department of Microbiology and Immunology, Institute of Biosciences, UNESP–Univ Estadual Paulista, Botucatu, São Paulo, Brazil
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  • Ramon Kaneno

    Corresponding author
    1. Department of Microbiology and Immunology, Institute of Biosciences, UNESP–Univ Estadual Paulista, Botucatu, São Paulo, Brazil
    2. Department of Pathology, School of Medicine, UNESP–Univ Estadual Paulista, Botucatu, São Paulo, Brazil
    • Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, UNESP. Cx Postal 510, Distrito de Rubião Jr. s/n, 18618-970, Botucatu, São Paulo, Brazil
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    • Tel.: [551438800432], Fax: +[55-14-38153744]


  • Conflict of interest: Authors declare that there is no conflict of interest.

Abstract

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy.

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