Editors' ChoiceImmunology

Uncovering a Hidden Talent

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Science Translational Medicine  24 Apr 2013:
Vol. 5, Issue 182, pp. 182ec68
DOI: 10.1126/scitranslmed.3006346

Chemotherapy is part of the standard treatment for many advanced cancers. Traditionally, it is thought to work by directly killing or inhibiting the growth of cancer cells. However, some chemotherapeutics appear to have hidden talents that may better explain their cancer-fighting abilities. In a recent study, Ma et al. explain how one class of chemotherapeutic agents, anthracyclines, may work by activating a potent antitumor immune response.

In a series of experiments, mice with intact immune systems were given mitoxantrone or doxorubicin—two anthracycline chemotherapies—to treat a diversity of implanted syngeneic tumors. The authors found that a population of myeloid cells rapidly accumulated in the tumor after systemic chemotherapy. Recruitment of these CD11c+CD11b+Ly6Chigh myeloid cells, which share some characteristics of inflammatory dendritic cells, depended on adenosine 5´-triphosphate (ATP) released from the dying cancer cells and on a type of purinergic receptor that permits monocytes to travel to the site of apoptotic cells. Ma et al. next tested the connection between the CD11c+CD11b+Ly6Chigh cells and the antitumor effects of anthracycline chemotherapy. First, by experimentally depleting or blocking the intratumoral accumulation of these cells, the authors abolished the antitumor activity of the chemotherapy. This effect was not seen when other dendritic cells populations were depleted. Second, the transfer of purified CD11c+CD11b+Ly6Chigh cells collected from tumor-bearing mice was able to confer protective immunity against subsequent tumor challenge to naïve mice. These two lines of evidence support the notion that the immune system, by using a specific a population of dendritic cells, is required for the antitumor activity of anthracylines.

Additional studies will be needed to see if anthracyclines bring about similar changes in human tumors and to compare anthracyclines with other chemotherapeutic agents. Nevertheless, Ma et al. have uncovered an important, immune-dependent mechanism of the activity for a very commonly used class of chemotherapy. By engaging the immune system, these agents appear to deliver a one-two punch, combining direct tumor cell–killing with immune protection against tumor growth.

Y. Ma et al., Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity. 38, 729–741 (2013). [Abstract]

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