Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy
Varsha Gadiyar,
Kevin C. Lahey,
David Calianese,
Connor Devoe,
Dhriti Mehta,
Kristy Bono,
Samuel Desind,
Viralkumar Davra,
Raymond B. Birge
Affiliations
Varsha Gadiyar
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Kevin C. Lahey
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
David Calianese
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Connor Devoe
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Dhriti Mehta
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Kristy Bono
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Samuel Desind
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Viralkumar Davra
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
Raymond B. Birge
Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, 205 South Orange Ave, Newark, NJ 07103, USA
The physiological fate of cells that die by apoptosis is their prompt and efficient removal by efferocytosis. During these processes, apoptotic cells release intracellular constituents that include purine nucleotides, lysophosphatidylcholine (LPC), and Sphingosine-1-phosphate (S1P) that induce migration and chemo-attraction of phagocytes as well as mitogens and extracellular membrane-bound vesicles that contribute to apoptosis-induced compensatory proliferation and alteration of the extracellular matrix and the vascular network. Additionally, during efferocytosis, phagocytic cells produce a number of anti-inflammatory and resolving factors, and, together with apoptotic cells, efferocytic events have a homeostatic function that regulates tissue repair. These homeostatic functions are dysregulated in cancers, where, aforementioned events, if not properly controlled, can lead to cancer progression and immune escape. Here, we summarize evidence that apoptosis and efferocytosis are exploited in cancer, as well as discuss current translation and clinical efforts to harness signals from dying cells into therapeutic strategies.
