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Dissertation/Thesis Abstract

The cellular and molecular origin of tumor-associated macrophages
by Franklin, Ruth Anne, Ph.D., Cornell University, 2014, 205; 3581371
Abstract (Summary)

Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases including cancer. Additionally, with the recent finding that macrophages originate from both embryonic and hematopoietic precursors, studies have begun to investigate macrophage ontogeny and the signals driving macrophage differentiation during steady state and disease. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). Although both macrophage populations originate from inflammatory monocytes, TAMs require fewer precursors for their maintenance due to a higher proliferative capacity compared to MTMs. TAMs express the adhesion molecule Vcam1, but do not exhibit the "alternatively activated" or "M2" macrophage phenotype that is often described in the tumor setting. Rather, MTMs appear to be phenotypically M2-polarized. TAM terminal differentiation from monocytes depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response with a non-redundant role in promoting tumor growth, potentially providing new opportunities for cancer immunotherapy.

Indexing (document details)
Advisor: Li, Ming
School: Cornell University
School Location: United States -- New York
Source: DAI-B 75/10(E), Dissertation Abstracts International
Subjects: Cellular biology, Immunology, Oncology
Publication Number: 3581371
ISBN: 978-1-321-13362-2
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