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Killing Is Not Enough: How Apoptosis Hijacks Tumor-Associated Macrophages to Promote Cancer Progression

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Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 930))

Abstract

Macrophages are a group of heterogeneous cells of the innate immune system that are crucial to the initiation, progression, and resolution of inflammation. Moreover, they control tissue homeostasis in healthy tissue and command a broad sensory arsenal to detect disturbances in tissue integrity. Macrophages possess a remarkable functional plasticity to respond to irregularities and to initiate programs that allow overcoming them in order to return back to normal. Thus, macrophages kill malignant or transformed cells, rearrange extracellular matrix, take up and recycle cellular as well as molecular debris, initiate cellular growth cascades, and favor directed migration of cells. As an example, apoptotic death of bystander cells is sensed by macrophages, initiating functional responses that support all hallmarks of cancer. In this chapter, we describe how tumor cell apoptosis hijacks tumor-associated macrophages to promote tumor growth. We propose that tumor therapy should not only kill malignant cells but also target the interaction of the host with apoptotic cancer cells, as this might be efficient to limit the protumor action of apoptotic cells and boost the antitumor potential of macrophages. Leaving the apoptotic cell/macrophage interaction untouched might also limit the benefit of conventional tumor cell apoptosis-focused therapy since surviving tumor cells might receive overwhelming support by the wound healing response that apoptotic tumor cells will trigger in local macrophages, thereby enhancing tumor recurrence.

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Acknowledgments

We gratefully acknowledge the following funding organizations: Deutsche Forschungsgemeinschaft (SFB 815, SFB 1039, BR999, and Excellence Cluster Cardiopulmonary System), Deutsche Krebshilfe (110637, 111578), Sander Foundation (2013.036.1), Else Kröner-Fresenius-Graduiertenkolleg and Translational Research Innovation - Pharma (TRIP) (both funded by the Else Kröner-Fresenius-Stiftung).

We apologize to researchers whose primary observations that form the basis of current knowledge in the field have been acknowledged indirectly, by referring to current reviews.

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  1. Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Andreas Weigert, Javier Mora, Divya Sekar, Shahzad Syed & Bernhard Brüne

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  1. Andreas Weigert
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  2. Javier Mora
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Correspondence to Bernhard Brüne .

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  1. MRC Centre for Inflammation Research, University of Edinburgh Queen’s Medical Research Institute, Edinburgh, United Kingdom

    Christopher D. Gregory

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Weigert, A., Mora, J., Sekar, D., Syed, S., Brüne, B. (2016). Killing Is Not Enough: How Apoptosis Hijacks Tumor-Associated Macrophages to Promote Cancer Progression. In: Gregory, C. (eds) Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy. Advances in Experimental Medicine and Biology, vol 930. Springer, Cham. https://doi.org/10.1007/978-3-319-39406-0_9

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