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Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects

Key Points

  • Chemotherapy, radiation, and molecularly targeted drugs generate host-mediated pro-tumorigenic and pro-metastatic effects that can contribute to cancer recurrence

  • Such therapy-induced host effects have been reported to support angiogenesis, metastasis, and tumour-cell repopulation and resistance to therapy

  • Host-derived tumour accessory cells and various secreted factors induced by cancer therapies can contribute to tumour recurrence during or following anticancer drug therapy

  • Blunting these cellular and molecular host-mediated effects generated by anticancer drugs might improve overall therapeutic outcomes

Abstract

Local and systemic treatments for cancer include surgery, radiation, chemotherapy, hormonal therapy, molecularly targeted therapies, antiangiogenic therapy, and immunotherapy. Many of these therapies can be curative in patients with early stage disease, but much less frequently is this the case when they are used to treat advanced-stage metastatic disease. In the latter setting, innate and/or acquired resistance are among the reasons for reduced responsiveness or nonresponsiveness to therapy, or for tumour relapse after an initial response. Most studies of resistance or reduced responsiveness focus on 'driver' genetic (or epigenetic) changes in the tumour-cell population. Several studies have highlighted the contribution of therapy-induced physiological changes in host tissues and cells that can reduce or even nullify the desired antitumour effects of therapy. These unwanted host effects can promote tumour-cell proliferation (repopulation) and even malignant aggressiveness. These effects occur as a result of systemic release of numerous cytokines, and mobilization of various host accessory cells, which can invade the treated tumour microenvironment. In short, the desired tumour-targeting effects of therapy (the 'yin') can be offset by a reactive host response (the 'yang'); proactively preventing or actively suppressing the latter represents a possible new approach to improving the efficacy of both local and systemic cancer therapies.

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Figure 1: The tumour promoting and inhibitory effects of anticancer agents: Yin and Yang effects.

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Acknowledgements

The work of the author is primarily supported by a grant kindly provided by the European Research Council under the FP-7 framework. The author apologizes for not including several additional studies related to this Review, owing to space limitations.

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Shaked, Y. Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects. Nat Rev Clin Oncol 13, 611–626 (2016). https://doi.org/10.1038/nrclinonc.2016.57

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