title: Killing Is Not Enough: How Apoptosis Hijacks Tumor-Associated Macrophages to Promote Cancer Progression.
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.
authors: Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors: Andreas
authors: A
authors: Weigert
authors: Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors: Javier
authors: J
authors: Mora
authors: Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors: Divya
authors: D
authors: Sekar
authors: Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors: Shahzad
authors: S
authors: Syed
authors: Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. b.bruene@biochem.uni-frankfurt.de.
authors: Bernhard
authors: B
authors: Brüne
mesh_terms: D000067531:Alarmins / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D008264:Macrophages / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D012334:RNA, Neoplasm / Q000235:genetics; D017211:Treatment Failure
chemical_list: D000067531:Alarmins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm
keywords: Apoptotic cells; Hallmarks of cancer; Macrophage polarization; Ontogeny of tumor macrophages; Role of tumor-associated macrophages; Tumor immunosuppression; Tumor stroma interaction; Tumor therapy directed against tumor-associated macrophages; Tumor-associated macrophages