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Apoptotic Cell Clearance in Health and Disease

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Front. Immunol. | doi: 10.3389/fimmu.2018.00241

Exploitation of Apoptotic Regulation in Cancer

  • 1Microbiology and Immunology, University of Illinois at Chicago, United States
  • 2Department of Medicine, University of Illinois at Chicago, United States
  • 3Jesse Brown VA Medical Center (VHA), United States

Within an organism, environmental stresses can trigger cell death, particularly apoptotic cell death. Apoptotic cells, themselves, are potent regulators of their cellular environment, involved primarily in effecting homeostatic control. Tumors, especially, exist in a dynamic balance of cell proliferation and cell death. This special feature of the tumorous microenvironment – namely, the prominence and persistence of cell death – necessarily entails a magnification of the extrinsic, post-mortem effects of dead cells. In both normal and malignant tissues, apoptotic regulation is exerted through immune as well as non-immune mechanisms. Apoptotic cells suppress the repertoire of immune reactivities, both by attenuating innate (especially inflammatory) responses and by abrogating adaptive responses. In addition, apoptotic cells modulate multiple vital cell activities, including survival, proliferation (cell number), and growth (cell size). While the microenvironment of the tumor may contribute to apoptosis, the post-mortem effects of apoptotic cells feature prominently in the reciprocal acclimatization between the tumor and its environment. In much the same way that pathogens evade the host's defenses through exploitation of key aspects of innate and adaptive immunity, cancer cells subvert several normal homeostatic processes, in particular wound healing and organ regeneration, to transform and overtake their environment. In understanding this subversion, it is crucial to view a tumor not simply as a clone of malignant cells, but rather as a complex and highly organized structure in which there exists a multidirectional flow of information between the cancer cells themselves and the multiple other cell types and extracellular matrix components of which the tumor is comprised. Apoptotic cells therefore have the unfortunate consequence of facilitating tumorigenesis and tumor survival.

Keywords: tumorigenesis, Apoptosis, microenvironment, Selective adaptation, Inflammation, Immunity

Received: 23 Oct 2017; Accepted: 29 Jan 2018.

Edited by:

Amiram Ariel, University of Haifa, Israel

Reviewed by:

Raymond B. Birge, Rutgers University, The State University of New Jersey, United States
Tal Burstyn-Cohen, Hebrew University of Jerusalem, Israel  

Copyright: © 2018 Ucker and Levine. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. David S. Ucker, University of Illinois at Chicago, Microbiology and Immunology, 835 South Wolcott Avenue (MC790), University of Illinois College of Medicine, Chicago, 60612, Illinois, United States,