Melanoma displays an evolutionarily conserved resistance to modulation of phagocytic signals
2017-08
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Melanoma displays an evolutionarily conserved resistance to modulation of phagocytic signals
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2017-08
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Therapeutic activation of macrophage phagocytosis has the ability to restrain tumor growth through phagocytic clearance of tumor cells and activation of the adaptive immune response. The objective of this thesis was to evaluate the effects of modulating pro- and anti-phagocytic pathways in malignant melanoma. We observed that melanoma cells from mice, humans, and dogs displayed an unexpected resistance to phagocytosis that could not be fully mitigated by blockade of the “don’t eat me” signal CD47 or by chemotherapeutic enhancement of known “eat me” signals. In addition, combination doxorubicin chemotherapy and CD47 blockade did not consistently promote an anti-tumor adaptive immune response. Phagocytosis of melanoma cells was not enhanced by inhibition of secretory pathways, and phagocytosis of sensitive lymphoma tumor cells was not impaired in the presence of melanoma culture supernatants, indicating that soluble factors did not mediate phagocytosis resistance. siRNA mediated knockdown of 47 candidate “don’t eat me” signals similarly did not enhance melanoma cell phagocytosis, suggesting that these proteins do not disable macrophage phagocytosis. We conclude melanoma cells possess a mechanism of resistance to phagocytosis. Further investigation will be needed to define this mechanism and to develop strategies to overcome melanoma cell resistance to the innate immune response.
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University of Minnesota Ph.D. dissertation. August 2017. Major: Comparative and Molecular Biosciences. Advisor: Jaime Modiano. 1 computer file (PDF); vi, 136 pages.
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Anderson, Katie. (2017). Melanoma displays an evolutionarily conserved resistance to modulation of phagocytic signals. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/191409.
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